当前期刊: Critical Reviews in Biochemistry and Molecular Biology Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • The ammonia-lyases: enzymes that use a wide range of approaches to catalyze the same type of reaction
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2020-01-06
    Ronald E. Viola

    The paradigm that protein structure determines protein function has been clearly established. What is less clear is whether a specific protein structure is always required to carry out a specific function. Numerous cases are now known where there is no apparent connection between the biological function of a protein and the other members of its structural class, and where functionally related proteins can have quite diverse structures. A set of enzymes with these diverse properties, the ammonia-lyases, will be examined in this review. These are a class of enzymes that catalyze a relatively straightforward deamination reaction. However, the individual enzymes of this class possess a wide variety of different structures, utilize a diverse set of cofactors, and appear to catalyze this related reaction through a range of different mechanisms. This review aims to address a basic question: if there is not a specific protein structure and active site architecture that is both required and sufficient to define a catalyst for a given chemical reaction, then what factor(s) determine the structure and the mechanism that is selected to catalyze a particular reaction?

    更新日期:2020-01-07
  • Structural and functional modularity of the U2 snRNP in pre-mRNA splicing
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-11-20
    Clarisse van der Feltz, Aaron A. Hoskins

    The U2 small nuclear ribonucleoprotein (snRNP) is an essential component of the spliceosome, the cellular machine responsible for removing introns from precursor mRNAs (pre-mRNAs) in all eukaryotes. U2 is an extraordinarily dynamic splicing factor and the most frequently mutated in cancers. Cryo-electron microscopy (cryo-EM) has transformed our structural and functional understanding of the role of U2 in splicing. In this review, we synthesize these and other data with respect to a view of U2 as an assembly of interconnected functional modules. These modules are organized by the U2 small nuclear RNA (snRNA) for roles in spliceosome assembly, intron substrate recognition, and protein scaffolding. We describe new discoveries regarding the structure of U2 components and how the snRNP undergoes numerous conformational and compositional changes during splicing. We specifically highlight large scale movements of U2 modules as the spliceosome creates and rearranges its active site. U2 serves as a compelling example for how cellular machines can exploit the modular organization and structural plasticity of an RNP.

    更新日期:2019-11-20
  • Spatiotemporal regulation of PCNA ubiquitination in damage tolerance pathways
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-11-18
    Yuji Masuda, Chikahide Masutani

    Abstract DNA is constantly exposed to a wide variety of exogenous and endogenous agents, and most DNA lesions inhibit DNA synthesis. To cope with such problems during replication, cells have molecular mechanisms to resume DNA synthesis in the presence of DNA lesions, which are known as DNA damage tolerance (DDT) pathways. The concept of ubiquitination-mediated regulation of DDT pathways in eukaryotes was established via genetic studies in the yeast Saccharomyces cerevisiae, in which two branches of the DDT pathway are regulated via ubiquitination of proliferating cell nuclear antigen (PCNA): translesion DNA synthesis (TLS) and homology-dependent repair (HDR), which are stimulated by mono- and polyubiquitination of PCNA, respectively. Over the subsequent nearly two decades, significant progress has been made in understanding the mechanisms that regulate DDT pathways in other eukaryotes. Importantly, TLS is intrinsically error-prone because of the miscoding nature of most damaged nucleotides and inaccurate replication of undamaged templates by TLS polymerases (pols), whereas HDR is theoretically error-free because the DNA synthesis is thought to be predominantly performed by pol δ, an accurate replicative DNA pol, using the undamaged sister chromatid as its template. Thus, the regulation of the choice between the TLS and HDR pathways is critical to determine the appropriate biological outcomes caused by DNA damage. In this review, we summarize our current understanding of the species-specific regulatory mechanisms of PCNA ubiquitination and how cells choose between TLS and HDR. We then provide a hypothetical model for the spatiotemporal regulation of DDT pathways in human cells.

    更新日期:2019-11-18
  • The multiscale effects of polycomb mechanisms on 3D chromatin folding
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-11-07
    Thierry Cheutin, Giacomo Cavalli

    Polycomb group (PcG) proteins silence master regulatory genes required to properly confer cell identity during the development of both Drosophila and mammals. They may act through chromatin compaction and higher-order folding of chromatin inside the cell nucleus. During the last decade, analysis on interphase chromosome architecture discovered self-interacting regions named topologically associated domains (TADs). TADs result from the 3D chromatin folding of a succession of transcribed and repressed epigenomic domains and from loop extrusion mediated by cohesin/CTCF in mammals. Polycomb silenced chromatin constitutes one type of repressed epigenomic domains which form compacted nano-compartments inside cell nuclei. Recruitment of canonical PcG proteins on chromatin relies on initial binding to discrete elements and further spreading into large chromatin domains covered with H3K27me3. Some of these discrete elements have a bivalent nature both in mammals and Drosophila and are dynamically regulated during development. Loops can occur between them, suggesting that their interaction plays both functional and structural roles. Formation of large chromatin domains covered by H3K27me3 seems crucial for PcG silencing and PcG proteins might exert their function through compaction of these domains in both mammals and flies, rather than by directly controlling the nucleosomal accessibility of discrete regulatory elements. In addition, PcG chromatin domains interact over long genomic distances, shaping a higher-order chromatin network. Therefore, PcG silencing might rely on multiscale chromatin folding to maintain cell identity during differentiation.

    更新日期:2019-11-08
  • Epigenetic changes during aging and their reprogramming potential.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-03-02
    Alice E Kane,David A Sinclair

    The aging process results in significant epigenetic changes at all levels of chromatin and DNA organization. These include reduced global heterochromatin, nucleosome remodeling and loss, changes in histone marks, global DNA hypomethylation with CpG island hypermethylation, and the relocalization of chromatin modifying factors. Exactly how and why these changes occur is not fully understood, but evidence that these epigenetic changes affect longevity and may cause aging, is growing. Excitingly, new studies show that age-related epigenetic changes can be reversed with interventions such as cyclic expression of the Yamanaka reprogramming factors. This review presents a summary of epigenetic changes that occur in aging, highlights studies indicating that epigenetic changes may contribute to the aging process and outlines the current state of research into interventions to reprogram age-related epigenetic changes.

    更新日期:2019-11-01
  • Resistance outside the substrate envelope: hepatitis C NS3/4A protease inhibitors.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-03-02
    Ayşegül Özen,Kristina Prachanronarong,Ashley N Matthew,Djade I Soumana,Celia A Schiffer

    Direct acting antivirals have dramatically increased the efficacy and tolerability of hepatitis C treatment, but drug resistance has emerged with some of these inhibitors, including nonstructural protein 3/4 A protease inhibitors (PIs). Although many co-crystal structures of PIs with the NS3/4A protease have been reported, a systematic review of these crystal structures in the context of the rapidly emerging drug resistance especially for early PIs has not been performed. To provide a framework for designing better inhibitors with higher barriers to resistance, we performed a quantitative structural analysis using co-crystal structures and models of HCV NS3/4A protease in complex with natural substrates and inhibitors. By comparing substrate structural motifs and active site interactions with inhibitor recognition, we observed that the selection of drug resistance mutations correlates with how inhibitors deviate from viral substrates in molecular recognition. Based on this observation, we conclude that guiding the design process with native substrate recognition features is likely to lead to more robust small molecule inhibitors with decreased susceptibility to resistance.

    更新日期:2019-11-01
  • Inhibition of farnesyl pyrophosphate (FPP) and/or geranylgeranyl pyrophosphate (GGPP) biosynthesis and its implication in the treatment of cancers.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-02-19
    Daniel D Waller,Jaeok Park,Youla S Tsantrizos

    Dysregulation of isoprenoid biosynthesis is implicated in numerous biochemical disorders that play a role in the onset and/or progression of age-related diseases, such as hypercholesterolemia, osteoporosis, various cancers, and neurodegeneration. The mevalonate metabolic pathway is responsible for the biosynthesis of the two key isoprenoid metabolites, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational prenylation of various proteins, including the small GTP-binding proteins (GTPases), with either FPP or GGPP is vital for proper localization and activation of these proteins. Prenylated GTPases play a critical role in cell signaling, proliferation, cellular plasticity, oncogenesis, and cancer metastasis. Pre-clinical and clinical studies strongly suggest that inhibition of protein prenylation can be an effective treatment for non-skeletal cancers. In this review, we summarize the most recent drug discovery efforts focusing on blocking protein farnesylation and/or geranylgeranylation and the biochemical and structural data available in guiding the current on-going studies in drug discovery. Furthermore, we provide a summary on the biochemical association between disruption of protein prenylation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR) signaling, and cancer.

    更新日期:2019-11-01
  • A tumor suppressive DNA translocase named FANCM.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-02-05
    Jihane Basbous,Angelos Constantinou

    FANCM is named after Fanconi anemia (FA) complement group M. The clinical symptoms of FA include congenital abnormalities, pancytopenia, and cancer proneness. However, recent studies reveal that biallelic inactivation of FANCM does not cause the constellation of FA symptoms, but predisposes patients to cancer and infertility. FANCM is a tumor suppressor gene that encodes a conserved and structure-specific DNA translocase. It controls the outcome of homologous recombination and facilitates DNA replication across a variety of natural and chemically induced obstacles. This review details our current understanding of FANCM as a facilitator of the cellular functions of caretaker proteins, including FA, Bloom syndrome, and Ataxia telangiectasia and RAD3-related proteins, which collectively ensure the maintenance of chromosome stability during DNA replication.

    更新日期:2019-11-01
  • The ZZ domain as a new epigenetic reader and a degradation signal sensor.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2019-01-30
    Yi Zhang,Wenyi Mi,Yongming Xue,Xiaobing Shi,Tatiana G Kutateladze

    Although relatively small in size, the ZZ-type zinc finger (ZZ) domain is a versatile signaling module that is implicated in a diverse set of cell signaling events. Here, we highlight the most recent studies focused on the ZZ domain function as a histone reader and a sensor of protein degradation signals. We review and compare the molecular and structural mechanisms underlying targeting the amino-terminal sequences of histone H3 and arginylated substrates by the ZZ domain. We also discuss the ZZ domain sensitivity to histone PTMs and summarize biological outcomes associated with the recognition of histone and non-histone ligands by the ZZ domain-containing proteins and complexes.

    更新日期:2019-11-01
  • Sources of spontaneous mutagenesis in bacteria.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2017-11-08
    Jeremy W Schroeder,Ponlkrit Yeesin,Lyle A Simmons,Jue D Wang

    Mutations in an organism's genome can arise spontaneously, that is, in the absence of exogenous stress and prior to selection. Mutations are often neutral or deleterious to individual fitness but can also provide genetic diversity driving evolution. Mutagenesis in bacteria contributes to the already serious and growing problem of antibiotic resistance. However, the negative impacts of spontaneous mutagenesis on human health are not limited to bacterial antibiotic resistance. Spontaneous mutations also underlie tumorigenesis and evolution of drug resistance. To better understand the causes of genetic change and how they may be manipulated in order to curb antibiotic resistance or the development of cancer, we must acquire a mechanistic understanding of the major sources of mutagenesis. Bacterial systems are particularly well-suited to studying mutagenesis because of their fast growth rate and the panoply of available experimental tools, but efforts to understand mutagenic mechanisms can be complicated by the experimental system employed. Here, we review our current understanding of mutagenic mechanisms in bacteria and describe the methods used to study mutagenesis in bacterial systems.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Riboactivators: transcription activation by noncoding RNA.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2009-03-13
    Aseem Z Ansari

    The paradigm of gene regulation was forever changed by the discovery that short RNA duplexes could directly regulate gene expression. Most regulatory roles attributed to noncoding RNA were often repressive. Recent observations are beginning to reveal that duplex RNA molecules can stimulate gene transcription. These RNA activators employ a wide array of mechanisms to up-regulate transcription of target genes, including functioning as DNA-tethered activation domains, as coactivators and modulators of general transcriptional machinery, and as regulators of other noncoding transcripts. The discoveries over the past few years defy "Moore's law" in the breath-taking rapidity with which new roles for noncoding RNA in gene expression are being revealed. As gene regulatory networks are reconstructed to accommodate the influence of noncoding RNAs, their importance in maintenance of cellular health will become increasingly apparent. In fact, a new generation of therapeutic agents will focus on modulating the function of noncoding RNA.

    更新日期:2019-11-01
  • SRA and its binding partners: an expanding role for RNA-binding coregulators in nuclear receptor-mediated gene regulation.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2009-03-13
    Shane M Colley,Peter J Leedman

    The discovery that SRA RNA can function as a nuclear receptor (NR) coactivator resulted in a fundamental change in the perception of how NRs and their coregulators may regulate hormone signaling pathways. The subsequent identification of molecules capable of binding SRA, including SHARP, p68, and more recently SLIRP, which also function as coregulators, has further broadened our understanding of NR-dependent gene regulation. The integral role that NRs play in directing developmental, metabolic and pathological programs of transcription has defined them as paramount targets for treating a broad range of human diseases. Thus with a greater understanding of SRA and its interactions with its binding partners, novel RNA-protein interactions may be identified and exploited for therapeutic gain. Here we discuss the isolation of SRA, its impact on NR activity and interactions with known binding partners.

    更新日期:2019-11-01
  • Nuclear RNA surveillance: no sign of substrates tailing off.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2009-03-13
    James T Anderson,Xuying Wang

    The production of cellular RNAs is tightly regulated to ensure gene expression is limited to appropriate times and locations. Elimination of RNA can be rapid and programmed to quickly terminate gene expression, or can be used to purge old, damaged or inappropriately formed RNAs. It is elimination of RNAs through the action of a polyadenylation complex (TRAMP), first described in the yeast Saccharomyces cerevisiae, which is the focus of this review. The discovery of TRAMP and presence of orthologs in most eukaryotes, along with an increasing number of potential TRAMP substrates in the form of new small non-coding RNAs, many of which emanate from areas of genomes once thought transcriptionally silent; promise to make this area of research of great interest for the foreseeable future.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • From bacteria to humans, chromatin to elongation, and activation to repression: The expanding roles of noncoding RNAs in regulating transcription.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-12-25
    James A Goodrich,Jennifer F Kugel

    Noncoding RNAs (ncRNAs) have emerged as key regulators of transcription, often functioning as trans-acting factors akin to prototypical protein transcriptional regulators. Inside cells, ncRNAs are now known to control transcription of single genes as well as entire transcriptional programs in response to developmental and environmental cues. In doing so, they target nearly all levels of the transcription process from regulating chromatin structure through controlling transcript elongation. Moreover, trans-acting ncRNA transcriptional regulators have been found in organisms as diverse as bacteria and humans. With the recent discovery that much of the DNA in genomes is transcribed into ncRNAs with yet unknown function, it is likely that future studies will reveal many more ncRNA regulators of transcription.

    更新日期:2019-11-01
  • RNA under attack: cellular handling of RNA damage.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-12-18
    Elisabeth J Wurtmann,Sandra L Wolin

    Damage to RNA from ultraviolet light, oxidation, chlorination, nitration, and akylation can include chemical modifications to nucleobases as well as RNA-RNA and RNA-protein crosslinking. In vitro studies have described a range of possible damage products, some of which are supported as physiologically relevant by in vivo observations in normal growth, stress conditions, or disease states. Damage to both messenger RNA and noncoding RNA may have functional consequences, and work has begun to elucidate the role of RNA turnover pathways and specific damage recognition pathways in clearing cells of these damaged RNAs.

    更新日期:2019-11-01
  • Diverse regulatory mechanisms of eukaryotic transcriptional activation by the proteasome complex.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-12-06
    Sukesh R Bhaumik,Shivani Malik

    The life of any protein within a cell begins with transcriptional activation, and ends with proteolytic degradation. Intriguingly, the 26S proteasome complex, a non-lysosomal protein degradation machine comprising the 20S proteolytic core and 19S regulatory particles, has been implicated in intimate regulation of eukaryotic transcriptional activation through diverse mechanisms in a proteolysis-dependent as well as independent manner. Here, we discuss the intricate mechanisms of such proteasomal regulation of eukaryotic gene activation via multiple pathways.

    更新日期:2019-11-01
  • The major architects of chromatin: architectural proteins in bacteria, archaea and eukaryotes.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-11-28
    Martijn S Luijsterburg,Malcolm F White,Roel van Driel,Remus Th Dame

    The genomic DNA of all organisms across the three kingdoms of life needs to be compacted and functionally organized. Key players in these processes are DNA supercoiling, macromolecular crowding and architectural proteins that shape DNA by binding to it. The architectural proteins in bacteria, archaea and eukaryotes generally do not exhibit sequence or structural conservation especially across kingdoms. Instead, we propose that they are functionally conserved. Most of these proteins can be classified according to their architectural mode of action: bending, wrapping or bridging DNA. In order for DNA transactions to occur within a compact chromatin context, genome organization cannot be static. Indeed chromosomes are subject to a whole range of remodeling mechanisms. In this review, we discuss the role of (i) DNA supercoiling, (ii) macromolecular crowding and (iii) architectural proteins in genome organization, as well as (iv) mechanisms used to remodel chromosome structure and to modulate genomic activity. We conclude that the underlying mechanisms that shape and remodel genomes are remarkably similar among bacteria, archaea and eukaryotes.

    更新日期:2019-11-01
  • Mechanisms of recombination: lessons from E. coli.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-11-19
    Nicole S Persky,Susan T Lovett

    The genetics and biochemistry of genetic recombination in E. coli has been studied for over four decades and provides a useful model system to understand recombination in other organisms. Here we provide an overview of the mechanisms of recombination and how such processes contribute to DNA repair. We describe the E. coli functions that are known to contribute to these mechanisms, step by step, and summarize their biochemical properties in relation to the role these proteins play in vivo. We feature areas of investigation that are newly emerging, as well as work that provides a historical perspective to the field. Finally, we highlight some of the questions that remain unanswered.

    更新日期:2019-11-01
  • Self-regulated Pax gene expression and modulation by the TGFbeta superfamily.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-11-19
    Victoria Frost,Timothy Grocott,Michael R Eccles,Andrew Chantry

    The mammalian Pax gene family encode a set of paired-domain transcription factors which play essential roles in regulating proliferation, differentiation, apoptosis, cell migration, and stem-cell maintenance. Pax gene expression is necessarily tightly controlled and is associated with the demarcation of boundaries during tissue development and specification. Auto- and inter-regulation are mechanisms frequently employed to achieve precise control of Pax expression domains in a variety of tissues including the eye, central nervous system, kidney, pancreas, skeletal system, muscle, tooth, and thymus. Furthermore, aberrant Pax expression is linked to several diseases and causally associated with certain tumors. An increasing number of studies also relate patterns of Pax expression to signaling by members of the TGFbeta superfamily and, in some instances, this is due to disruption of Pax gene auto-regulation. Here, we review the current evidence highlighting functional and mechanistic overlap between TGFbeta signaling and Pax-mediated gene transcription. We conclude that self-regulation of Pax gene expression coupled with modulation by the TGFbeta superfamily represents a signaling axis that is frequently employed during development and disease to drive normal tissue growth, differentiation and homeostasis.

    更新日期:2019-11-01
  • SSB as an organizer/mobilizer of genome maintenance complexes.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-10-22
    Robert D Shereda,Alexander G Kozlov,Timothy M Lohman,Michael M Cox,James L Keck

    When duplex DNA is altered in almost any way (replicated, recombined, or repaired), single strands of DNA are usually intermediates, and single-stranded DNA binding (SSB) proteins are present. These proteins have often been described as inert, protective DNA coatings. Continuing research is demonstrating a far more complex role of SSB that includes the organization and/or mobilization of all aspects of DNA metabolism. Escherichia coli SSB is now known to interact with at least 14 other proteins that include key components of the elaborate systems involved in every aspect of DNA metabolism. Most, if not all, of these interactions are mediated by the amphipathic C-terminus of SSB. In this review, we summarize the extent of the eubacterial SSB interaction network, describe the energetics of interactions with SSB, and highlight the roles of SSB in the process of recombination. Similar themes to those highlighted in this review are evident in all biological systems.

    更新日期:2019-11-01
  • Structure and mechanism of metallocarboxypeptidases.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-10-22
    F Xavier Gomis-Rüth

    Metallocarboxpeptidases cleave C-terminal residues from peptide substrates and participate in a wide range of physiological processes, but they also contribute to human pathology. On the basis of structural information, we can distinguish between two groups of such metallopeptidases: cowrins and funnelins. Cowrins comprise protozoan, prokaryotic, and mammalian enzymes related to both neurolysin and angiotensin-converting enzyme and their catalytic domains contain 500-700 residues. They are ellipsoidal and traversed horizontally by a long, deep, narrow active-site cleft, in which the C-terminal residues are cut from oligopeptides and unstructured protein tails. The consensus cowrin structure contains a common core of 17 helices and a three-stranded beta-sheet, which participates in substrate binding. This protease family is characterized by a set of spatially conserved amino acids involved in catalysis, HEXXH+EXXS/G+H+Y/R+Y. Funnelins comprise structural relatives of the archetypal bovine carboxypeptidase A1 and feature mammalian, insect and bacterial proteins with strict carboxypeptidase activity. Their approximately 300-residue catalytic domains evince a consensus central eight-stranded beta-sheet flanked on either side by a total of eight helices. They also contain a characteristic set of conserved residues, HXXE+R+NR+H+Y+E, and their active-site clefts are rather shallow and lie at the bottom of a funnel-like cavity. Therefore, these enzymes act on a large variety of well-folded proteins. In both cowrins and funnelins, substrate hydrolysis follows a common general base/acid mechanism. A metal-bound solvent molecule ultimately performs the attack on the scissile peptide bond with the assistance of a strictly conserved glutamate residue.

    更新日期:2019-11-01
  • TOR signaling in fission yeast.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-08-30
    Yoko Otsubo,Masayuki Yamamato

    Fission yeast has two TOR kinases, Tor1 and Tor2. Recent studies have indicated that this microbe has a TSC/Rheb/TOR pathway like higher eukaryotes. Two TOR complexes, namely TORC1 and TORC2, have been identified in this yeast, as in budding yeast and mammals. Fission yeast TORC1, which contains Tor2, and TORC2, which contains Tor1, apparently have opposite functions with regard to the promotion of G1 arrest and sexual development. Rapamycin does not inhibit growth of wild-type fission yeast cells, unlike other eukaryotic cells, but precise analyses have revealed that rapamycin affects certain cellular functions involving TOR in this yeast. It appears that fission yeast has a potential to be an ideal model system to investigate the TOR signaling pathways.

    更新日期:2019-11-01
  • Base excision repair and its role in maintaining genome stability.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-08-30
    Joke Baute,Anne Depicker

    For all living organisms, genome stability is important, but is also under constant threat because various environmental and endogenous damaging agents can modify the structural properties of DNA bases. As a defense, organisms have developed different DNA repair pathways. Base excision repair (BER) is the predominant pathway for coping with a broad range of small lesions resulting from oxidation, alkylation, and deamination, which modify individual bases without large effect on the double helix structure. As, in mammalian cells, this damage is estimated to account daily for 10(4) events per cell, the need for BER pathways is unquestionable. The damage-specific removal is carried out by a considerable group of enzymes, designated as DNA glycosylases. Each DNA glycosylase has its unique specificity and many of them are ubiquitous in microorganisms, mammals, and plants. Here, we review the importance of the BER pathway and we focus on the different roles of DNA glycosylases in various organisms.

    更新日期:2019-11-01
  • Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-06-24
    Judith M White,Sue E Delos,Matthew Brecher,Kathryn Schornberg

    Recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. In addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. Viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. These differing features combine to yield a rich diversity of fusion proteins. Yet despite this staggering diversity, all characterized viral fusion proteins convert from a fusion-competent state (dimers or trimers, depending on the class) to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide, attached to the target membrane, and the transmembrane domain, attached to the viral membrane, into close proximity thereby facilitating the union of viral and target membranes. During these conformational conversions, the fusion proteins induce membranes to progress through stages of close apposition, hemifusion, and then the formation of small, and finally large, fusion pores. Clearly, highly divergent proteins have converged on the same overall strategy to mediate fusion, an essential step in the life cycle of every enveloped virus.

    更新日期:2019-11-01
  • Deinococcus radiodurans: what belongs to the survival kit?
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-06-24
    Melanie Blasius,Suzanne Sommer,Ulrich Hübscher

    Deinococcus radiodurans, one of the most radioresistant organisms known to date, is able to repair efficiently hundreds of DNA double- and single-strand breaks as well as other types of DNA damages promoted by ionizing or ultraviolet radiation. We review recent discoveries concerning several aspects of radioresistance and survival under high genotoxic stress. We discuss different hypotheses and possibilities that have been suggested to contribute to radioresistance and propose that D. radiodurans combines a variety of physiological tools that are tightly coordinated. A complex network of regulatory proteins may be discovered in the near future that might allow further understanding of radioresistance.

    更新日期:2019-11-01
  • AAA+ ATPases in the initiation of DNA replication.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-06-24
    Karl E Duderstadt,James M Berger

    All cellular organisms and many viruses rely on large, multi-subunit molecular machines, termed replisomes, to ensure that genetic material is accurately duplicated for transmission from one generation to the next. Replisome assembly is facilitated by dedicated initiator proteins, which serve to both recognize replication origins and recruit requisite replisomal components to the DNA in a cell-cycle coordinated manner. Exactly how imitators accomplish this task, and the extent to which initiator mechanisms are conserved among different organisms have remained outstanding issues. Recent structural and biochemical findings have revealed that all cellular initiators, as well as the initiators of certain classes of double-stranded DNA viruses, possess a common adenine nucleotide-binding fold belonging to the ATPases Associated with various cellular Activities (AAA+) family. This review focuses on how the AAA+ domain has been recruited and adapted to control the initiation of DNA replication, and how the use of this ATPase module underlies a common set of initiator assembly states and functions. How biochemical and structural properties correlate with initiator activity, and how species-specific modifications give rise to unique initiator functions, are also discussed.

    更新日期:2019-11-01
  • Regulation of maternal mRNAs in early development.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-03-28
    Brian M Farley,Sean P Ryder

    Most sexually reproducing metazoans are anisogamous, meaning that the two gametes that combine during fertilization differ greatly in size. By convention, the larger gametes are considered female and are called ova, while the smaller gametes are male and are called sperm. In most cases, both gametes contribute similarly to the chromosomal content of the new organism. In contrast, the maternal gamete contributes nearly all of the cytoplasm. This cytoplasmic contribution is crucial to patterning early development; it contains the maternal proteins and transcripts that guide the early steps of development prior to the activation of zygotic transcription. This review compares and contrasts early development in common laboratory model organisms in order to highlight the similarities and differences in the regulation of maternal factors. We will focus on the production and reversible silencing of maternal mRNAs during oogenesis, their asymmetric activation after fertilization, and their subsequent clearance at the midblastula transition. Where possible, insights from mechanistic studies are presented.

    更新日期:2019-11-01
  • The bacterial chromosome.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-03-28
    Milton H Saier

    Bacteria represent the vast majority of biological diversity found on Earth. In this review, we focus on selected aspects of their genetic material, those providing insight into structural, functional, dynamic, and evolutionary aspects of their genomes. Bacterial chromosomes are far more dynamic than previously realized, and dozens of mechanisms giving rise to genomic plasticity are now understood. Maturation of the genomics era has provided the tools for unraveling the interwoven details of DNA structure/function relationships that provide a basis for organismal diversity. Some of the most throughly understood processes that underlie the dynamics of genomic structure and function in prokaryotes are examined.

    更新日期:2019-11-01
  • The Drosophila circadian pacemaker circuit: Pas De Deux or Tarantella?
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-03-01
    Vasu Sheeba,Maki Kaneko,Vijay Kumar Sharma,Todd C Holmes

    Molecular genetic analysis of the fruit fly Drosophila melanogaster has revolutionized our understanding of the transcription/translation loop mechanisms underlying the circadian molecular oscillator. More recently, Drosophila has been used to understand how different neuronal groups within the circadian pacemaker circuit interact to regulate the overall behavior of the fly in response to daily cyclic environmental cues as well as seasonal changes. Our present understanding of circadian timekeeping at the molecular and circuit level is discussed with a critical evaluation of the strengths and weaknesses of present models. Two models for circadian neural circuits are compared: one that posits that two anatomically distinct oscillators control the synchronization to the two major daily morning and evening transitions, versus a distributed network model that posits that many cell-autonomous oscillators are coordinated in a complex fashion and respond via plastic mechanisms to changes in environmental cues.

    更新日期:2019-11-01
  • The Radical SAM Superfamily.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-03-01
    Perry A Frey,Adrian D Hegeman,Frank J Ruzicka

    The radical S-adenosylmethionine (SAM) superfamily currently comprises more than 2800 proteins with the amino acid sequence motif CxxxCxxC unaccompanied by a fourth conserved cysteine. The charcteristic three-cysteine motif nucleates a [4Fe-4S] cluster, which binds SAM as a ligand to the unique Fe not ligated to a cysteine residue. The members participate in more than 40 distinct biochemical transformations, and most members have not been biochemically characterized. A handful of the members of this superfamily have been purified and at least partially characterized. Significant mechanistic and structural information is available for lysine 2,3-aminomutase, pyruvate formate-lyase, coproporphyrinogen III oxidase, and MoaA required for molybdopterin biosynthesis. Biochemical information is available for spore photoproduct lyase, anaerobic ribonucleotide reductase activation subunit, lipoyl synthase, and MiaB involved in methylthiolation of isopentenyladenine-37 in tRNA. The radical SAM enzymes biochemically characterized to date have in common the cleavage of the [4Fe-4S](1 +) -SAM complex to [4Fe-4S](2 +)-Met and the 5' -deoxyadenosyl radical, which abstracts a hydrogen atom from the substrate to initiate a radical mechanism.

    更新日期:2019-11-01
  • CLC chloride channels and transporters: from genes to protein structure, pathology and physiology.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2008-03-01
    Thomas J Jentsch

    CLC genes are expressed in species from bacteria to human and encode Cl(-)-channels or Cl(-)/H(+)-exchangers. CLC proteins assemble to dimers, with each monomer containing an ion translocation pathway. Some mammalian isoforms need essential beta -subunits (barttin and Ostm1). Crystal structures of bacterial CLC Cl(-)/H(+)-exchangers, combined with transport analysis of mammalian and bacterial CLCs, yielded surprising insights into their structure and function. The large cytosolic carboxy-termini of eukaryotic CLCs contain CBS domains, which may modulate transport activity. Some of these have been crystallized. Mammals express nine CLC isoforms that differ in tissue distribution and subcellular localization. Some of these are plasma membrane Cl(-) channels, which play important roles in transepithelial transport and in dampening muscle excitability. Other CLC proteins localize mainly to the endosomal-lysosomal system where they may facilitate luminal acidification or regulate luminal chloride concentration. All vesicular CLCs may be Cl(-)/H(+)-exchangers, as shown for the endosomal ClC-4 and -5 proteins. Human diseases and knockout mouse models have yielded important insights into their physiology and pathology. Phenotypes and diseases include myotonia, renal salt wasting, kidney stones, deafness, blindness, male infertility, leukodystrophy, osteopetrosis, lysosomal storage disease and defective endocytosis, demonstrating the broad physiological role of CLC-mediated anion transport.

    更新日期:2019-11-01
  • Glycan antagonists and inhibitors: a fount for drug discovery.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-12-11
    Jillian R Brown,Brett E Crawford,Jeffrey D Esko

    Glycans, the carbohydrate chains of glycoproteins, proteoglycans, and glycolipids, represent a relatively unexploited area for drug development compared with other macromolecules. This review describes the major classes of glycans synthesized by animal cells, their mode of assembly, and available inhibitors for blocking their biosynthesis and function. Many of these agents have proven useful for studying the biological activities of glycans in isolated cells, during embryological development, and in physiology. Some are being used to develop drugs for treating metabolic disorders, cancer, and infection, suggesting that glycans are excellent targets for future drug development.

    更新日期:2019-11-01
  • Encoding olfactory signals via multiple chemosensory systems.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-12-11
    Minghong Ma

    Most animals have evolved multiple olfactory systems to detect general odors as well as social cues. The sophistication and interaction of these systems permit precise detection of food, danger, and mates, all crucial elements for survival. In most mammals, the nose contains two well described chemosensory apparatuses (the main olfactory epithelium and the vomeronasal organ), each of which comprises several subtypes of sensory neurons expressing distinct receptors and signal transduction machineries. In many species (e.g., rodents), the nasal cavity also includes two spatially segregated clusters of neurons forming the septal organ of Masera and the Grueneberg ganglion. Results of recent studies suggest that these chemosensory systems perceive diverse but overlapping olfactory cues and that some neurons may even detect the pressure changes carried by the airflow. This review provides an update on how chemosensory neurons transduce chemical (and possibly mechanical) stimuli into electrical signals, and what information each system brings into the brain. Future investigation will focus on the specific ligands that each system detects with a behavioral context and the processing networks that each system involves in the brain. Such studies will lead to a better understanding of how the multiple olfactory systems, acting in concert, offer a complete representation of the chemical world.

    更新日期:2019-11-01
  • Role of type 2C protein phosphatases in growth regulation and in cellular stress signaling.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-12-11
    Twan Lammers,Sara Lavi

    A number of interesting features, phenotypes, and potential clinical applications have recently been ascribed to the type 2C family of protein phosphatases. Thus far, 16 different PP2C genes have been identified in the human genome, encoding (by means of alternative splicing) for at least 22 different isozymes. Virtually ever since their discovery, type 2C phosphatases have been predominantly linked to cell growth and to cellular stress signaling. Here, we provide an overview of the involvement of type 2C phosphatases in these two processes, and we show that four of them (PP2Calpha, PP2Cbeta, ILKAP, and PHLPP) can be expected to function as tumor suppressor proteins, and one as an oncoprotein (PP2Cdelta /Wip1). In addition, we demonstrate that in virtually all cases in which they have been linked to the stress response, PP2Cs act as inhibitors of cellular stress signaling. Based on the vast amount of experimental evidence obtained thus far, it therefore seems justified to conclude that type 2C protein phosphatases are important physiological regulators of cell growth and of cellular stress signaling.

    更新日期:2019-11-01
  • Mutation as a stress response and the regulation of evolvability.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-10-06
    Rodrigo S Galhardo,P J Hastings,Susan M Rosenberg

    Our concept of a stable genome is evolving to one in which genomes are plastic and responsive to environmental changes. Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially accelerating adaptive evolution. The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes. The first is the regulation of mutagenesis in time by cellular stress responses, which promote random mutations specifically when cells are poorly adapted to their environments, i.e., when they are stressed. A second theme is the possible restriction of random mutagenesis in genomic space, achieved via coupling of mutation-generating machinery to local events such as DNA-break repair or transcription. Such localization may minimize accumulation of deleterious mutations in the genomes of rare fitter mutants, and promote local concerted evolution. Although mutagenesis induced by stresses other than direct damage to DNA was previously controversial, evidence for the existence of various stress-induced mutagenesis programs is now overwhelming and widespread. Such mechanisms probably fuel evolution of microbial pathogenesis and antibiotic-resistance, and tumor progression and chemotherapy resistance, all of which occur under stress, driven by mutations. The emerging commonalities in stress-induced-mutation mechanisms provide hope for new therapeutic interventions for all of these processes.

    更新日期:2019-11-01
  • Stress-induced mutagenesis in bacteria.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-10-06
    Patricia L Foster

    Bacteria spend their lives buffeted by changing environmental conditions. To adapt to and survive these stresses, bacteria have global response systems that result in sweeping changes in gene expression and cellular metabolism. These responses are controlled by master regulators, which include: alternative sigma factors, such as RpoS and RpoH; small molecule effectors, such as ppGpp; gene repressors such as LexA; and, inorganic molecules, such as polyphosphate. The response pathways extensively overlap and are induced to various extents by the same environmental stresses. These stresses include nutritional deprivation, DNA damage, temperature shift, and exposure to antibiotics. All of these global stress responses include functions that can increase genetic variability. In particular, up-regulation and activation of error-prone DNA polymerases, down-regulation of error-correcting enzymes, and movement of mobile genetic elements are common features of several stress responses. The result is that under a variety of stressful conditions, bacteria are induced for genetic change. This transient mutator state may be important for adaptive evolution.

    更新日期:2019-11-01
  • The Hsp90 capacitor, developmental remodeling, and evolution: the robustness of gene networks and the curious evolvability of metamorphosis.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-10-06
    Suzannah Rutherford,Yoshikazu Hirate,Billie J Swalla

    Genetic capacitors moderate expression of heritable variation and provide a novel mechanism for rapid evolution. The prototypic genetic capacitor, Hsp90, interfaces stress responses, developmental networks, trait thresholds and expression of wide-ranging morphological changes in Drosophila and other organisms. The Hsp90 capacitor hypothesis, that stress-sensitive storage and release of genetic variation through Hsp90 facilitates adaptive evolution in unpredictable environments, has been challenged by the belief that Hsp90-buffered variation is unconditionally deleterious. Here we review recent results supporting the Hsp90 capacitor hypothesis, highlighting the heritability, selectability, and potential evolvability of Hsp90-buffered traits. Despite a surprising bias toward morphological novelty and typically invariable quantitative traits, Hsp90-buffered changes are remarkably modular, and can be selected to high frequency independent of the expected negative side-effects or obvious correlated changes in other, unselected traits. Recent dissection of cryptic signal transduction variation involved in one Hsp90-buffered trait reveals potentially dozens of normally silent polymorphisms embedded in cell cycle, differentiation and growth control networks. Reduced function of Hsp90 substrates during environmental stress would destabilize robust developmental processes, relieve developmental constraints and plausibly enables genetic network remodeling by abundant cryptic alleles. We speculate that morphological transitions controlled by Hsp90 may fuel the incredible evolutionary lability of metazoan life-cycles.

    更新日期:2019-11-01
  • Genetic constraints on protein evolution.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-10-06
    Manel Camps,Asael Herman,Ern Loh,Lawrence A Loeb

    Evolution requires the generation and optimization of new traits ("adaptation") and involves the selection of mutations that improve cellular function. These mutations were assumed to arise by selection of neutral mutations present at all times in the population. Here we review recent evidence that indicates that deleterious mutations are more frequent in the population than previously recognized and that these mutations play a significant role in protein evolution through continuous positive selection. Positively selected mutations include adaptive mutations, i.e. mutations that directly affect enzymatic function, and compensatory mutations, which suppress the pleiotropic effects of adaptive mutations. Compensatory mutations are by far the most frequent of the two and would allow potentially adaptive but deleterious mutations to persist long enough in the population to be positively selected during episodes of adaptation. Compensatory mutations are, by definition, context-dependent and thus constrain the paths available for evolution. This provides a mechanistic basis for the examples of highly constrained evolutionary landscapes and parallel evolution reported in natural and experimental populations. The present review article describes these recent advances in the field of protein evolution and discusses their implications for understanding the genetic basis of disease and for protein engineering in vitro.

    更新日期:2019-11-01
  • Controlling mutation: intervening in evolution as a therapeutic strategy.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-10-06
    Ryan T Cirz,Floyd E Romesberg

    Mutation is the driving force behind many processes linked to human disease, including cancer, aging, and the evolution of drug resistance. Mutations have traditionally been considered the inevitable consequence of replicating large genomes with polymerases of finite fidelity. Observations over the past several decades, however, have led to a new perspective on the process of mutagenesis. It has become clear that, under some circumstances, mutagenesis is a regulated process that requires the induction of pro-mutagenic enzymes and that, at least in bacteria, this induction may facilitate evolution. Herein, we review what is known about induced mutagenesis in bacteria as well as evidence that it contributes to the evolution of antibiotic resistance. Finally, we discuss the possibility that components of induced mutation pathways might be targeted for inhibition as a novel therapeutic strategy to prevent the evolution of antibiotic resistance.

    更新日期:2019-11-01
  • Stationary phase mutagenesis in B. subtilis: a paradigm to study genetic diversity programs in cells under stress.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-10-06
    Eduardo A Robleto,Ronald Yasbin,Christian Ross,Mario Pedraza-Reyes

    One of the experimental platforms to study programs increasing genetic diversity in cells under stressful or nondividing conditions is adaptive mutagenesis, also called stationary phase mutagenesis or stress-induced mutagenesis. In some model systems, there is evidence that mutagenesis occurs in genes that are actively transcribed. Some of those genes may be actively transcribed as a result of environmental stress giving the appearance of directed mutation. That is, cells under conditions of starvation or other stresses accumulate mutations in transcribed genes, including those transcribed because of the selective pressure. An important question concerns how, within the context of stochastic processes, a cell biases mutation to genes under selection pressure? Because the mechanisms underlying DNA transactions in prokaryotic cells are well conserved among the three domains of life, these studies are likely to apply to the examination of genetic programs in eukaryotes. In eukaryotes, increasing genetic diversity in differentiated cells has been implicated in neoplasia and cell aging. Historically, Escherichia coli has been the paradigm used to discern the cellular processes driving the generation of adaptive mutations; however, examining adaptive mutation in Bacillus subtilis has contributed new insights. One noteworthy contribution is that the B. subtilis' ability to accumulate chromosomal mutations under conditions of starvation is influenced by cell differentiation and transcriptional derepression, as well as by proteins homologous to transcription and repair factors. Here we revise and discuss concepts pertaining to genetic programs that increase diversity in B. subtilis cells under nutritional stress.

    更新日期:2019-11-01
  • Adaptive mutation in Saccharomyces cerevisiae.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-08-10
    Erich Heidenreich

    Adaptive mutation is a generic term for processes that allow individual cells of nonproliferating cell populations to acquire advantageous mutations and thereby to overcome the strong selective pressure of proliferation-limiting environmental conditions. Prerequisites for an occurrence of adaptive mutation are that the selective conditions are nonlethal and that a restart of proliferation may be accomplished by some genetic change in principle. The importance of adaptive mutation is derived from the assumption that it may, on the one hand, result in an accelerated evolution of microorganisms and, on the other, in multicellular organisms may contribute to a breakout of somatic cells from negative growth regulation, i.e., to cancerogenesis. Most information on adaptive mutation in eukaryotes has been gained with the budding yeast Saccharomyces cerevisiae. This review focuses comprehensively on adaptive mutation in this organism and summarizes our current understanding of this issue.

    更新日期:2019-11-01
  • Adaptive amplification.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-08-10
    P J Hastings

    Modern techniques are revealing that repetition of segments of the genome, called amplification or gene amplification, is very common. Amplification is found in all domains of life, and occurs under conditions where enhanced expression of the amplified genes is advantageous. Amplification extends the range of gene expression beyond that which is achieved by control systems. It also is reversible because it is unstable, breaking down by homologous recombination. Amplification is believed to be the driving force in the clustering of related functions, in that it allows them to be amplified together. Amplification provides the extra copies of genes that allow evolution of functions to occur while retaining the original function. Amplification can be induced in response to cellular stressors. In many cases, it has been shown that the genomic regions that are amplified include those genes that are appropriate to upregulate for a specific stressor. There is some evidence that amplification occurs as part of a broad, general stress response, suggesting that organisms have the capacity to induce structural changes in the genome. This then allows adaptation to the stressful conditions. The mechanisms by which amplification arises are now being studied at the molecular level, but much is still unknown about the mechanisms in all organisms. Recent advances in our understanding of amplification in bacteria suggests new interpretations of events leading to human copy number variation, as well as evolution in general.

    更新日期:2019-11-01
  • Too many mutants with multiple mutations.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-08-10
    John W Drake

    It has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a random distribution of mutations. Excesses of multiples are seen in a wide range of organisms, including riboviruses, DNA viruses, prokaryotes, yeasts, and higher eukaryotic cell lines and tissues. In addition, such excesses are produced by DNA polymerases in vitro. These "multiples" appear to be generated by transient, localized hypermutation rather than by heritable mutator mutations. The components of multiples are sometimes scattered at random and sometimes display an excess of smaller distances between mutations. As yet, almost nothing is known about the mechanisms that generate multiples, but such mutations have the capacity to accelerate those evolutionary pathways that require multiple mutations where the individual mutations are neutral or deleterious. Examples that impinge on human health may include carcinogenesis and the adaptation of microbial pathogens as they move between individual hosts.

    更新日期:2019-11-01
  • Causes and consequences of DNA repair activity modulation during stationary phase in Escherichia coli.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-08-10
    Claude Saint-Ruf,Josipa Pesut,Mary Sopta,Ivan Matic

    Escherichia coli responds to nutrient exhaustion by entering a state commonly referred to as the stationary phase. Cells entering the stationary phase redirect metabolic circuits to scavenge any available nutrients and become resistant to different stresses. However, many DNA repair pathways are downregulated in stationary-phase cells, which results in increased mutation rates. DNA repair activity generally depends on consumption of energy and often requires de novo proteins synthesis. Consequently, unless stringently regulated during stationary phase, DNA repair activities may lead to an irreversible depletion of energy sources and, therefore to cell death. Most stationary phase morphological and physiological modifications are regulated by an alternative RNA polymerase sigma factor RpoS. However, nutrient availability, and the frequency and nature of stresses, are different in distinct environmental niches, which impose conflicting choices that result in selection of the loss or of the modification of RpoS function. Consequently, DNA repair activity, which is partially controlled by RpoS, is differently modulated in different environments. This results in the variable mutation rates among different E. coli ecotypes. Hence, the polymorphism of mutation rates in natural E. coli populations can be viewed as a byproduct of the selection for improved fitness.

    更新日期:2019-11-01
  • Protein degradation within mitochondria: versatile activities of AAA proteases and other peptidases.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-06-15
    Mirko Koppen,Thomas Langer

    Cell survival depends on essential processes in mitochondria. Various proteases within these organelles regulate mitochondrial biogenesis and ensure the complete degradation of excess or damaged proteins. Many of these proteases are highly conserved and ubiquitous in eukaryotic cells. They can be assigned to three functional classes: processing peptidases, which cleave off mitochondrial targeting sequences of nuclearly encoded proteins and process mitochondrial proteins with regulatory functions; ATP-dependent proteases, which either act as processing peptidases with regulatory functions or as quality-control enzymes degrading non-native polypeptides to peptides; and oligopeptidases, which degrade these peptides and mitochondrial targeting sequences to amino acids. Disturbances of protein degradation within mitochondria cause severe phenotypes in various organisms and can lead to the induction of apoptotic programmes and cell-specific neurodegeneration in mammals. After an overview of the proteolytic system of mitochondria, we will focus on versatile functions of ATP-dependent AAA proteases in the inner membrane. These conserved proteolytic machines conduct protein quality surveillance of mitochondrial inner membrane proteins, mediate vectorial protein dislocation from membranes, and, acting as processing enzymes, control ribosome assembly, mitochondrial protein synthesis, and mitochondrial fusion. Implications of these functions for cell-specific axonal degeneration in hereditary spastic paraplegia will be discussed.

    更新日期:2019-11-01
  • The weird and wonderful world of bacterial ribosome regulation.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-06-15
    Daniel N Wilson,Knud H Nierhaus

    In every organism, translation of the genetic information into functional proteins is performed on the ribosome. In Escherichia coli up to 40% of the cell's total energy turnover is channelled toward the ribosome and protein synthesis. Thus, elaborate networks of translation regulation pathways have evolved to modulate gene expression in response to growth rate and external factors, ranging from nutrient deprivation, to chemical (pH, ionic strength) and physical (temperature) fluctuations. Since the fundamental players involved in regulation of the different phases of translation have already been extensively reviewed elsewhere, this review focuses on lesser known and characterized factors that regulate the ribosome, ranging from processing, modification and assembly factors, unusual initiation and elongation factors, to a variety of stress response proteins.

    更新日期:2019-11-01
  • The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-06-15
    Bénédicte Cauwe,Philippe E Van den Steen,Ghislain Opdenakker

    Matrix metalloproteinases (MMPs) constitute a family of more than 20 endopeptidases. Identification of specific matrix and non-matrix components as MMP substrates showed that, aside from their initial role as extracellular matrix modifiers, MMPs play significant roles in highly complex processes such as the regulation of cell behavior, cell-cell communication, and tumor progression. Thanks to the comprehensive examination of the expanded MMP action radius, the initial view of proteases acting in the soluble phase has evolved into a kaleidoscope of proteolytic reactions connected to the cell surface. Important classes of cell surface molecules include adhesion molecules, mediators of apoptosis, receptors, chemokines, cytokines, growth factors, proteases, intercellular junction proteins, and structural molecules. Proteolysis of cell surface proteins by MMPs may have extremely diverse biological implications, ranging from maturation and activation, to inactivation or degradation of substrates. In this way, modification of membrane-associated proteins by MMPs is crucial for communication between cells and the extracellular milieu, and determines cell fate and the integrity of tissues. Hence, insights into the processing of cell surface proteins by MMPs and the concomitant effects on physiological processes as well as on disease onset and evolution, leads the way to innovative therapeutic approaches for cancer, as well as degenerative and inflammatory diseases.

    更新日期:2019-11-01
  • Molecular chaperones HscA/Ssq1 and HscB/Jac1 and their roles in iron-sulfur protein maturation.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-04-25
    Larry E Vickery,Jill R Cupp-Vickery

    Genetic and biochemical studies have led to the identification of several cellular pathways for the biosynthesis of iron-sulfur proteins in different organisms. The most broadly distributed and highly conserved system involves an Hsp70 chaperone and J-protein co-chaperone system that interacts with a scaffold-like protein involved in [FeS]-cluster preassembly. Specialized forms of Hsp70 and their co-chaperones have evolved in bacteria (HscA, HscB) and in certain fungi (Ssq1, Jac1), whereas most eukaryotes employ a multifunctional mitochondrial Hsp70 (mtHsp70) together with a specialized co-chaperone homologous to HscB/Jac1. HscA and Ssq1 have been shown to specifically bind to a conserved sequence present in the [FeS]-scaffold protein designated IscU in bacteria and Isu in fungi, and the crystal structure of a complex of a peptide containing the IscU recognition region bound to the HscA substrate binding domain has been determined. The interaction of IscU/Isu with HscA/Ssq1 is regulated by HscB/Jac1 which bind the scaffold protein to assist delivery to the chaperone and stabilize the chaperone-scaffold complex by enhancing chaperone ATPase activity. The crystal structure of HscB reveals that the N-terminal J-domain involved in regulation of HscA ATPase activity is similar to other J-proteins, whereas the C-terminal domain is unique and appears to mediate specific interactions with IscU. At the present time the exact function(s) of chaperone-[FeS]-scaffold interactions in iron-sulfur protein biosynthesis remain(s) to be established. In vivo and in vitro studies of yeast Ssq1 and Jac1 indicate that the chaperones are not required for [FeS]-cluster assembly on Isu. Recent in vitro studies using bacterial HscA, HscB and IscU have shown that the chaperones destabilize the IscU[FeS] complex and facilitate cluster delivery to an acceptor apo-protein consistent with a role in regulating cluster release and transfer. Additional genetic and biochemical studies are needed to extend these findings to mtHsp70 activities in higher eukaryotes.

    更新日期:2019-11-01
  • Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA metabolism.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-04-25
    Zbigniew Dominski

    Proteins of the metallo-beta-lactamase family with either demonstrated or predicted nuclease activity have been identified in a number of organisms ranging from bacteria to humans and has been shown to be important constituents of cellular metabolism. Nucleases of this family are believed to utilize a zinc-dependent mechanism in catalysis and function as 5' to 3' exonucleases and or endonucleases in such processes as 3' end processing of RNA precursors, DNA repair, V(D)J recombination, and telomere maintenance. Examples of metallo-beta-lactamase nucleases include CPSF-73, a known component of the cleavage/polyadenylation machinery, which functions as the endonuclease in 3' end formation of both polyadenylated and histone mRNAs, and Artemis that opens DNA hairpins during V(D)J recombination. Mutations in two metallo-beta-lactamase nucleases have been implicated in human diseases: tRNase Z required for 3' processing of tRNA precursors has been linked to the familial form of prostate cancer, whereas inactivation of Artemis causes severe combined immunodeficiency (SCID). There is also a group of as yet uncharacterized proteins of this family in bacteria and archaea that based on sequence similarity to CPSF-73 are predicted to function as nucleases in RNA metabolism. This article reviews the cellular roles of nucleases of the metallo-beta-lactamase family and the recent advances in studying these proteins.

    更新日期:2019-11-01
  • Regulation of bacterial RecA protein function.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-03-17
    Michael M Cox

    The RecA protein is a recombinase functioning in recombinational DNA repair in bacteria. RecA is regulated at many levels. The expression of the recA gene is regulated within the SOS response. The activity of the RecA protein itself is autoregulated by its own C-terminus. RecA is also regulated by the action of other proteins. To date, these include the RecF, RecO, RecR, DinI, RecX, RdgC, PsiB, and UvrD proteins. The SSB protein also indirectly affects RecA function by competing for ssDNA binding sites. The RecO and RecR, and possibly the RecF proteins, all facilitate RecA loading onto SSB-coated ssDNA. The RecX protein blocks RecA filament extension, and may have other effects on RecA activity. The DinI protein stabilizes RecA filaments. The RdgC protein binds to dsDNA and blocks RecA access to dsDNA. The PsiB protein, encoded by F plasmids, is uncharacterized, but may inhibit RecA in some manner. The UvrD helicase removes RecA filaments from RecA. All of these proteins function in a network that determines where and how RecA functions. Additional regulatory proteins may remain to be discovered. The elaborate regulatory pattern is likely to be reprised for RecA homologues in archaeans and eukaryotes.

    更新日期:2019-11-01
  • A conspicuous connection: structure defines function for the phosphatidylinositol-phosphate kinase family.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-03-17
    Jessica N Heck,David L Mellman,Kun Ling,Yue Sun,Matthew P Wagoner,Nicholas J Schill,Richard A Anderson

    The phosphatidylinositol phosphate (PIP) kinases are a unique family of enzymes that generate an assortment of lipid messengers, including the pivotal second messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2). While members of the PIP kinase family function by catalyzing a similar phosphorylation reaction, the specificity loop of each PIP kinase subfamily determines substrate preference and partially influences distinct subcellular targeting. Specific protein-protein interactions that are unique to particular isoforms or splice variants play a key role in targeting PIP kinases to appropriate subcellular compartments to facilitate the localized generation of PI4,5P2 proximal to effectors, a mechanism key for the function of PI4,5P2 as a second messenger. This review documents the discovery of the PIP kinases and their signaling products, and summarizes our current understanding of the mechanisms underlying the localized generation of PI4,5P2 by PIP kinases for the regulation of cellular events including actin cytoskeleton dynamics, vesicular trafficking, cell migration, and an assortment of nuclear events.

    更新日期:2019-11-01
  • GABAA receptors: properties and trafficking.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2007-03-17
    Guido Michels,Stephen J Moss

    Fast synaptic inhibition in the brain and spinal cord is mediated largely by ionotropic gamma-aminobutyric acid (GABA) receptors. GABAA receptors play a key role in controlling neuronal activity; thus modulating their function will have important consequences for neuronal excitation. GABAA receptors are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are involved in a number of CNS diseases, including sleep disturbances, anxiety, premenstrual syndrome, alcoholism, muscle spasms, Alzheimer's disease, chronic pain, schizophrenia, bipolar affective disorders, and epilepsy. This review focuses on the functional and pharmacological properties of GABAA receptors and trafficking as an essential mechanism underlying the dynamic regulation of synaptic strength.

    更新日期:2019-11-01
  • Transpososome dynamics and regulation in Tn10 transposition.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2006-11-10
    David B Haniford

    Tn10 is a bacterial transposon that transposes through a non-replicative mechanism. This mode of DNA transposition is widely used in bacteria and is also used by "DNA-based" transposons in eukaryotes. Tn10 has served as a paradigm for this mode of transposition and continues to provide novel insights into how steps in transposition reactions occur and how these steps are regulated. A common feature of transposition reactions is that they require the formation of a higher order protein-DNA complex called a transpososome. A major objective in the last few years has been to better understand the dynamics of transpososome assembly and progression through the course of transposition reactions. This problem is particularly interesting in the Tn10 system because two important host proteins, IHF and H-NS, have been implicated in regulating transpososome assembly and/or function. Interestingly, H-NS is an integral part of stress response pathways in bacteria, and its function is known to be sensitive to changes in environmental conditions. Consequently, H-NS may provide a means of allowing Tn10 to responed to changing environmental conditions. The current review focuses on the roles of both IHF and H-NS on Tn10 transposition.

    更新日期:2019-11-01
  • The mu transpososome through a topological lens.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2006-11-10
    Rasika M Harshey,Makkuni Jayaram

    Phage Mu is the most efficient transposable element known, its high efficiency being conferred by an enhancer DNA element. Transposition is the end result of a series of well choreographed steps that juxtapose the enhancer and the two Mu ends within a nucleoprotein complex called the 'transpososome.' The particular arrangement of DNA and protein components lends extraordinary stability to the transpososome and regulates the frequency, precision, directionality, and mechanism of transposition. The structure of the transpososome, therefore, holds the key to understanding all of these attributes, and ultimately to explaining the runaway genetic success of transposable elements throughout the biological world. This review focuses on the path of the DNA within the Mu transpososome, as uncovered by recent topological analyses. It discusses why Mu topology cannot be analyzed by standard methods, and how knowledge of the geometry of site alignment during Flp and Cre site-specific recombination was harnessed to design a new methodology called 'difference topology.' This methodology has also revealed the order and dynamics of association of the three interacting DNA sites, as well as the role of the enhancer in assembly of the Mu transpososome.

    更新日期:2019-11-01
  • Signal integration during development: mechanisms of EGFR and Notch pathway function and cross-talk.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2006-11-10
    David B Doroquez,Ilaria Rebay

    Metazoan development relies on a highly regulated network of interactions between conserved signal transduction pathways to coordinate all aspects of cell fate specification, differentiation, and growth. In this review, we discuss the intricate interplay between the epidermal growth factor receptor (EGFR; Drosophila EGFR/DER) and the Notch signaling pathways as a paradigm for signal integration during development. First, we describe the current state of understanding of the molecular architecture of the EGFR and Notch signaling pathways that has resulted from synergistic studies in vertebrate, invertebrate, and cultured cell model systems. Then, focusing specifically on the Drosophila eye, we discuss how cooperative, sequential, and antagonistic relationships between these pathways mediate the spatially and temporally regulated processes that generate this sensory organ. The common themes underlying the coordination of the EGFR and Notch pathways appear to be broadly conserved and should, therefore, be directly applicable to elucidating mechanisms of information integration and signaling specificity in vertebrate systems.

    更新日期:2019-11-01
  • From ribosome to riboswitch: control of gene expression in bacteria by RNA structural rearrangements.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2006-11-10
    Frank J Grundy,Tina M Henkin

    Structural elements in the 5' region of a bacterial mRNA can have major effects on expression of downstream coding sequences. Folding of the nascent RNA into the helix of an intrinsic transcriptional terminator results in premature termination of transcription and in failure to synthesize the full-length transcript. Structure in the translation initiation region of an mRNA blocks access of the translation initiation complex to the ribosome binding site, thereby preventing protein synthesis. RNA structures can also affect the stability of an RNA by altering sensitivity to ribonucleases. A wide variety of mechanisms have been uncovered in which changes in mRNA structure in response to a regulatory signal are used to modulate gene expression in bacteria. These systems allow the cell to recognize an impressive array of signals, and to monitor those signals in many different ways.

    更新日期:2019-11-01
  • Proteome-scale analysis of biochemical activity.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2006-08-17
    Eric M Phizicky,Elizabeth J Grayhack

    During the last 10 years, there has been a large increase in the number of genome sequences available for study, altering the way that the biology of organisms is studied. In particular, scientific attention has increasingly focused on the proteome, and specifically on the role of all the proteins encoded by the genome. We focus here on several aspects of this problem. We describe several technologies in widespread use to clone genes on a genome-wide scale, and to express and purify the proteins encoded by these genes. We also describe a number of methods that have been developed to analyze various biochemical properties of the proteins, with attention to the methodology and the limitations of the approaches, followed by a look at possible developments in the next decade.

    更新日期:2019-11-01
  • The structure and function of frataxin.
    Crit. Rev. Biochem. Mol. Biol. (IF 6.069) Pub Date : 2006-08-17
    Krisztina Z Bencze,Kalyan C Kondapalli,Jeremy D Cook,Stephen McMahon,César Millán-Pacheco,Nina Pastor,Timothy L Stemmler

    Frataxin, a highly conserved protein found in prokaryotes and eukaryotes, is required for efficient regulation of cellular iron homeostasis. Humans with a frataxin deficiency have the cardio- and neurodegenerative disorder Friedreich's ataxia, commonly resulting from a GAA trinucleotide repeat expansion in the frataxin gene. While frataxin's specific function remains a point of controversy, the general consensus is that the protein assists in controlling cellular iron homeostasis by directly binding iron. This review focuses on the structural and biochemical aspects of iron binding by the frataxin orthologs and outlines molecular attributes that may help explain the protein's role in different cellular pathways.

    更新日期:2019-11-01
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
中国科学院微生物研究所潘国辉
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug