显示样式:     当前期刊: Trends in Biochemical Sciences    加入关注    导出
  • Oxa1 Superfamily: New Members Found in the ER
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2018-01-12
    Yuanyuan Chen, Ross E. Dalbey

    Oxa1/Alb3/YidC family members promote the insertion of proteins into the mitochondrial inner membrane, the chloroplast thylakoid membrane, and the bacterial plasma membrane. Remarkably, two recent studies identify new Oxa1 homologs that reside in the endoplasmic reticulum (ER) and function in ER membrane protein biogenesis.

  • Replication-Coupled Nucleosome Assembly in the Passage of Epigenetic Information and Cell Identity
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-29
    Albert Serra-Cardona, Zhiguo Zhang

    During S phase, replicated DNA must be assembled into nucleosomes using both newly synthesized and parental histones in a process that is tightly coupled to DNA replication. This DNA replication-coupled process is regulated by multitude of histone chaperones as well as by histone-modifying enzymes. In recent years novel insights into nucleosome assembly of new H3–H4 tetramers have been gained through studies on the classical histone chaperone CAF-1 and the identification of novel factors involved in this process. Moreover, in vitro reconstitution of chromatin replication has shed light on nucleosome assembly of parental H3–H4, a process that remains elusive. Finally, recent studies have revealed that the replication-coupled nucleosome assembly is important for the determination and maintenance of cell fate in multicellular organisms.

  • Resolving the Gordian Knot: Srs2 Strips Intermediates Formed during Homologous Recombination
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-28
    Harshad Ghodke, Jacob S. Lewis, Antoine M. van Oijen

    Cells use a suite of specialized enzymes to repair chromosomal double-strand breaks (DSBs). Two recent studies describe how single-molecule fluorescence imaging techniques are used in the direct visualization of some of the key molecular steps involved. De Tullio et al. and Kaniecki et al. watch individual Srs2 helicase molecules disrupt repair intermediates formed by RPA, Rad51, and Rad52 on DNA during homologous recombination.

  • Paraspeckles: Where Long Noncoding RNA Meets Phase Separation
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-27
    Archa H. Fox, Shinichi Nakagawa, Tetsuro Hirose, Charles S. Bond

    Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles – protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA–protein and protein–protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings.

  • MK2–TNF–Signaling Comes Full Circle
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-21
    Manoj B. Menon, Matthias Gaestel

    MK2 (p38MAPK-activated protein kinase 2) is essential for tumor necrosis factor (TNF) biosynthesis, mainly operating by post-transcriptional regulation. Deletion of the gene encoding MK2 strongly reduced serum TNF and protected against endotoxic shock, demonstrating the positive role of p38MAPK/MK2 in TNF signaling at the level of ligand expression. Recent evidence indicates that MK2 directly phosphorylates the TNF receptor interactor RIPK1 and suppresses its activity, thereby limiting TNF-mediated apoptosis and necroptosis – pointing to a more complex, double-edged role of MK2 in TNF signaling. In addition, novel MK2 substrates have emerged in the DNA damage response, autophagy, and obesity, making MK2 a multifunctional kinase at the crossroads of stress response and cell death. We therefore propose a more general role of p38MAPK/MK2 signaling in the timely coordinated onset and resolution of inflammation and beyond.

  • TCR Signaling: Mechanisms of Initiation and Propagation
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-18
    Adam H. Courtney, Wan-Lin Lo, Arthur Weiss

    The mechanisms by which a T cell detects antigen using its T cell antigen receptor (TCR) are crucial to our understanding of immunity and the harnessing of T cells therapeutically. A hallmark of the T cell response is the ability of T cells to quantitatively respond to antigenic ligands derived from pathogens while remaining inert to similar ligands derived from host tissues. Recent studies have revealed exciting properties of the TCR and the behaviors of its signaling effectors that are used to detect and discriminate between antigens. Here we highlight these recent findings, focusing on the proximal TCR signaling molecules Zap70, Lck, and LAT, to provide mechanistic models and insights into the exquisite sensitivity and specificity of the TCR.

  • Organization and Function of Non-dynamic Biomolecular Condensates
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-16
    Jeffrey B. Woodruff, Anthony A. Hyman, Elvan Boke

    Cells compartmentalize biochemical reactions using organelles. Organelles can be either membrane-bound compartments or supramolecular assemblies of protein and ribonucleic acid known as ‘biomolecular condensates’. Biomolecular condensates, such as nucleoli and germ granules, have been described as liquid like, as they have the ability to fuse, flow, and undergo fission. Recent experiments have revealed that some liquid-like condensates can mature over time to form stable gels. In other cases, biomolecular condensates solidify into amyloid-like fibers. Here we discuss the assembly, organization, and physiological roles of these more stable condensates in cells, focusing on Balbiani bodies, centrosomes, nuclear pores, and amyloid bodies. We discuss how the material properties of these condensates can be explained by the principles of liquid–liquid phase separation and maturation.

  • Hippo Signaling in the Immune System
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-14
    Yuchao Zhang, Haitao Zhang, Bin Zhao

    Hippo signaling has a pivotal role in organ size control, tissue regeneration, and cancer. Recent studies have demonstrated critical functions of Hippo signaling in cancer immunity, innate immune responses against pathogens, and autoimmune diseases, refreshing our understanding of the implications of this pathway in the context of disease and therapy design.

  • Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-14
    Wolfgang Dubiel, Dawadschargal Dubiel, Dieter A. Wolf, Michael Naumann

    Specificity of the ubiquitin proteasome system is controlled by ubiquitin E3 ligases, including their major representatives, the multisubunit cullin-RING ubiquitin (Ub) ligases (CRLs). More than 200 different CRLs are divided into seven families according to their cullin scaffolding proteins (CUL1–7) around which they are assembled. Research over two decades has revealed that different CRL families are specialized to fulfill specific cellular functions. Whereas many CUL1-based CRLs (CRL1s) ubiquitylate cell cycle regulators, CRL4 complexes often associate with chromatin to control DNA metabolism. Based on studies about differentiation programs of mesenchymal stem cells (MSCs), including myogenesis, neurogenesis, chondrogenesis, osteogenesis and adipogenesis, we propose here that CRL3 complexes evolved to fulfill a pivotal role in mammalian cell differentiation.

  • N-term 2017: Proteostasis via the N-terminus
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-09
    Nico Dissmeyer, Emmanuelle Graciet, Michael J. Holdsworth, Daniel J. Gibbs

    N-term 2017 was the first international meeting to bring together researchers from diverse disciplines with a shared interest in protein N-terminal modifications and the N-end rule pathway of ubiquitin-mediated proteolysis, providing a platform for interdisciplinary cross-kingdom discussions and collaborations, as well as strengthening the visibility of this growing scientific community.

  • The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-12-05
    Walid A. Houry, Edouard Bertrand, Benoit Coulombe

    The Rvb1–Rvb2–Tah1–Pih1/prefoldin-like (R2TP/PFDL) complex is a unique chaperone that provides a platform for the assembly and maturation of many key multiprotein complexes in mammalian cells. Here, we propose to rename R2TP/PFDL as PAQosome (particle for arrangement of quaternary structure) to more accurately represent its unique function.

  • Clustering of Rac1: Selective Lipid Sorting Drives Signaling
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-30
    Kelsey N. Maxwell, Yong Zhou, John F. Hancock

    The ability of lipid-anchored small GTPases to form nanometer-scale lipid domains on the cell plasma membrane (PM) is precipitating exciting new insights into membrane-anchored protein regulation. A recent article by Remorino et al. demonstrates that Rac1, similar to Ras, forms nanoclusters on the PM. The implications of these findings are discussed herein.

  • Paving TRAIL’s Path with Ubiquitin
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-28
    Elodie Lafont, Torsten Hartwig, Henning Walczak

    Despite its name, signalling induced by the tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is versatile. Besides eliciting cell death by both apoptosis and necroptosis, TRAIL can also induce migration, proliferation, and cytokine production in cancerous and non-cancerous cells. Unravelling the mechanisms regulating the intricate balance between these different outputs could therefore facilitate our understanding of the role of TRAIL in tissue homeostasis, immunity, and cancer. Ubiquitination and its reversal, deubiquitination, are crucial modulators of immune receptor signalling. This review discusses recent progress on the orchestration of TRAIL signalling outcomes by ubiquitination of various components of the signalling complexes, our understanding of the molecular switches that decide between cell death and gene activation, and what remains to be discovered.

  • Stereochemical Divergence of Polyprenol Phosphate Glycosyltransferases
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-25
    Jerry Eichler, Barbara Imperiali

    In the three domains of life, lipid-linked glycans contribute to various cellular processes ranging from protein glycosylation to glycosylphosphatidylinositol anchor biosynthesis to peptidoglycan assembly. In generating many of these glycoconjugates, phosphorylated polyprenol-based lipids are charged with single sugars by polyprenol phosphate glycosyltransferases. The resultant substrates serve as glycosyltransferase donors, complementing the more common nucleoside diphosphate sugars. It had been accepted that these polyprenol phosphate glycosyltransferases acted similarly, given their considerable sequence homology. Recent findings, however, suggest that matters may not be so simple. In this Opinion we propose that the stereochemistry of sugar addition by polyprenol phosphate glycosyltransferases is not conserved across evolution, even though the GT-A fold that characterizes such enzymes is omnipresent.

  • Immune Responses – Transcriptional and Post-Transcriptional Networks Pass the Baton
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-24
    Johannes Lichti, Christian Gallus, Elke Glasmacher

    Diverse gene regulatory mechanisms impact on immune homeostasis, and a new model now emerges as fundamental in light of recent genome-wide studies. In this picture, transcriptional networks drive functional changes during immune activation, whereas autoregulatory feedback loops of post-transcriptional programs ensure the original cell lineage identity and subsequent immune resolution.

  • Spatiotemporal Control of Acetyl-CoA Metabolism in Chromatin Regulation
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-23
    Sharanya Sivanand, Isabella Viney, Kathryn E. Wellen

    The epigenome is sensitive to the availability of metabolites that serve as substrates of chromatin-modifying enzymes. Links between acetyl-CoA metabolism, histone acetylation, and gene regulation have been documented, although how specificity in gene regulation is achieved by a metabolite has been challenging to answer. Recent studies suggest that acetyl-CoA metabolism is tightly regulated both spatially and temporally to elicit responses to nutrient availability and signaling cues. Here we discuss evidence that acetyl-CoA production is differentially regulated in the nucleus and cytosol of mammalian cells. Recent findings indicate that acetyl-CoA availability for site-specific histone acetylation is influenced through post-translational modification of acetyl-CoA-producing enzymes, as well as through dynamic regulation of the nuclear localization and chromatin recruitment of these enzymes.

  • Opposing Functions of Heparanase-1 and Heparanase-2 in Cancer Progression
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-20
    Israel Vlodavsky, Miriam Gross-Cohen, Marina Weissmann, Neta Ilan, Ralph D. Sanderson

    Heparanase, the sole heparan sulfate (HS)-degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby regulating the bioavailability of heparin-binding proteins; priming the tumor microenvironment; mediating tumor–host crosstalk; and inducing gene transcription, signaling pathways, exosome formation, and autophagy that together promote tumor cell performance and chemoresistance. By contrast, heparanase-2, a close homolog of heparanase, lacks enzymatic activity, inhibits heparanase activity, and regulates selected genes that promote normal differentiation, endoplasmic reticulum stress, tumor fibrosis, and apoptosis, together resulting in tumor suppression. The emerging premise is that heparanase is a master regulator of the aggressive phenotype of cancer, while heparanase-2 functions as a tumor suppressor.

  • How Are Proteins Reduced in the Endoplasmic Reticulum?
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-15
    Lars Ellgaard, Carolyn S. Sevier, Neil J. Bulleid

    The reversal of thiol oxidation in proteins within the endoplasmic reticulum (ER) is crucial for protein folding, degradation, chaperone function, and the ER stress response. Our understanding of this process is generally poor but progress has been made. Enzymes performing the initial reduction of client proteins, as well as the ultimate electron donor in the pathway, have been identified. Most recently, a role for the cytosol in ER protein reduction has been revealed. Nevertheless, how reducing equivalents are transferred from the cytosol to the ER lumen remains an open question. We review here why proteins are reduced in the ER, discuss recent data on catalysis of steps in the pathway, and consider the implications for redox homeostasis within the early secretory pathway.

  • Extending the Structural View of Class B GPCRs
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-11
    Chris de Graaf, Gaojie Song, Can Cao, Qiang Zhao, Ming-Wei Wang, Beili Wu, Raymond C. Stevens

    The secretin-like class B family of G protein-coupled receptors (GPCRs) are key players in hormonal homeostasis. Recent structures of various receptors in complex with a variety of orthosteric and allosteric ligands provide fundamental new insights into the function and mechanism of class B GPCRs, including: (i) ligand-induced changes in the relative orientation of the extracellular and transmembrane receptor domains; (ii) intramolecular interaction networks that stabilize conformational changes to accommodate intracellular G protein binding; and (iii) allosteric modulation of receptor activation. This review provides a comprehensive analysis of the structural, biochemical, and pharmacological data on class B GPCRs for understanding ligand–receptor interaction and modulation mechanisms and assessing the potential implications for drug discovery for the secretin-like GPCR family.

  • Hidden Secrets of Sigma54 Promoters Revealed
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-07
    Nan Hao, Keith E. Shearwin

    Bacterial sigma54 (σ54) promoters are the DNA-binding motif for σ54-containing RNA polymerase (RNAP) holoenzymes. A recent study using a combination of synthetic oligonucleotide library screening, biochemical characterization, and bioinformatics has uncovered a new and unexpected role for σ54 promoters, encoding a form of bacterial ‘insulator sequence’ to dampen unwanted translation.

  • Histone Marks in the ‘Driver’s Seat’: Functional Roles in Steering the Transcription Cycle
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-06
    Leah A. Gates, Charles E. Foulds, Bert W. O’Malley

    Particular chromatin modifications are associated with different states of gene transcription, yet our understanding of which modifications are causal ‘drivers’ in promoting transcription is incomplete. Here, we discuss new developments describing the ordered, mechanistic role of select histone marks occurring during distinct steps in the RNA polymerase II (Pol II) transcription cycle. In particular, we highlight the interplay between histone marks in specifying the ‘next step’ of transcription. While many studies have described correlative relationships between histone marks and their occupancy at distinct gene regions, we focus on studies that elucidate clear functional consequences of specific histone marks during different stages of transcription. These recent discoveries have refined our current mechanistic understanding of how histone marks promote Pol II transcriptional progression.

  • Cracking the Chaperone Code: Cellular Roles for Hsp70 Phosphorylation
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-11-05
    Nitika, Andrew W. Truman

    Heat shock protein 70 (Hsp70) is a molecular chaperone required for protein folding, cell viability, and cancer cell proliferation. Recent studies suggest that Hsp70 phosphorylation regulates important cellular processes, such as cell cycle progression, apoptosis, protein degradation, and resistance to anticancer therapeutics.

  • The Unsolved Problem of How Cells Sense Micron-Scale Curvature
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-10-28
    Kevin S. Cannon, Benjamin L. Woods, Amy S. Gladfelter

    Membrane curvature is a fundamental feature of cells and their organelles. Much of what we know about how cells sense curved surfaces comes from studies examining nanometer-sized molecules on nanometer-scale curvatures. We are only just beginning to understand how cells recognize curved topologies at the micron scale. In this review, we provide the reader with an overview of our current understanding of how cells sense and respond to micron-scale membrane curvature.

  • Outer Membrane Protein OmpB Methylation May Mediate Bacterial Virulence
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-10-13
    David C.H. Yang, Amila H. Abeykoon, Bok-Eum Choi, Wei-Mei Ching, P. Boon Chock

    Methylation of outer membrane proteins (OMPs) has been implicated in bacterial virulence. Lysine methylation in rickettsial OmpB is correlated with rickettsial virulence, and N- and O-methylations are also observed in virulence-relevant OMPs from several pathogenic bacteria that cause typhus, leptospirosis, tuberculosis, and anaplasmosis. We summarize recent findings on the structure of methylated OmpB, biochemical characterization, and crystal structures of OmpB methyltransferases. Native rickettsial OmpB purified from highly virulent strains contains multiple clusters of trimethyllysine, in contrast with mostly monomethyllysine, and no trimethyllysine is found in an avirulent strain. Crystal structure of the methyltransferases reveals mechanistic insights for catalysis, and a working model is discussed for this unusual post-translational modification.

  • Visualizing Nuclear RNA Editing
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-28
    Hodaya Hochberg, Yaron Shav-Tal

    RNA editing results in the site-specific conversion of adenosine to inosine in mRNAs. Genomics has revealed millions of editing sites in metazoans, but examining the spatial aspects of editing in cells has been challenging. A new method, inosineFISH (inoFISH), provides the ability to detect edited and unedited mRNAs within intact cells.

  • Sharing the SAGA
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-27
    Dominique Helmlinger, László Tora

    Transcription initiation is a major regulatory step in eukaryotic gene expression. Co-activators establish transcriptionally competent promoter architectures and chromatin signatures to allow the formation of the pre-initiation complex (PIC), comprising RNA polymerase II (Pol II) and general transcription factors (GTFs). Many GTFs and co-activators are multisubunit complexes, in which individual components are organized into functional modules carrying specific activities. Recent advances in affinity purification and mass spectrometry analyses have revealed that these complexes often share functional modules, rather than containing unique components. This observation appears remarkably prevalent for chromatin-modifying and remodeling complexes. Here, we use the modular organization of the evolutionary conserved Spt-Ada-Gcn5 acetyltransferase (SAGA) complex as a paradigm to illustrate how co-activators share and combine a relatively limited set of functional tools.

  • Regulation of the Hippo Pathway Transcription Factor TEAD
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-27
    Kimberly C. Lin, Hyun Woo Park, Kun-Liang Guan

    The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway. However, recent studies suggest that TEAD itself is actively regulated. Here, we highlight evidence demonstrating Hippo-independent regulation of TEADs and the potential impacts these studies may have on new cancer therapeutics.

  • The Ubiquitin Code in the Ubiquitin-Proteasome System and Autophagy
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-22
    Yong Tae Kwon, Aaron Ciechanover

    The conjugation of the 76 amino acid protein ubiquitin to other proteins can alter the metabolic stability or non-proteolytic functions of the substrate. Once attached to a substrate (monoubiquitination), ubiquitin can itself be ubiquitinated on any of its seven lysine (Lys) residues or its N-terminal methionine (Met1). A single ubiquitin polymer may contain mixed linkages and/or two or more branches. In addition, ubiquitin can be conjugated with ubiquitin-like modifiers such as SUMO or small molecules such as phosphate. The diverse ways to assemble ubiquitin chains provide countless means to modulate biological processes. We overview here the complexity of the ubiquitin code, with an emphasis on the emerging role of linkage-specific degradation signals (degrons) in the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system (hereafter autophagy).

  • Biochemistry of Mitochondrial Coenzyme Q Biosynthesis
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-17
    Jonathan A. Stefely, David J. Pagliarini

    Coenzyme Q (CoQ, ubiquinone) is a redox-active lipid produced across all domains of life that functions in electron transport and oxidative phosphorylation and whose deficiency causes human diseases. Yet, CoQ biosynthesis has not been fully defined in any organism. Several proteins with unclear molecular functions facilitate CoQ biosynthesis through unknown means, and multiple steps in the pathway are catalyzed by currently unidentified enzymes. Here we highlight recent progress toward filling these knowledge gaps through both traditional biochemistry and cutting-edge ‘omics’ approaches. To help fill the remaining gaps, we present questions framed by the recently discovered CoQ biosynthetic complex and by putative biophysical barriers. Mapping CoQ biosynthesis, metabolism, and transport pathways has great potential to enhance treatment of numerous human diseases.

  • Biochemical Mechanisms of Pathogen Restriction by Intestinal Bacteria
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-17
    Kavita J. Rangan, Howard C. Hang

    The intestine is a highly complex ecosystem where many bacterial species interact with each other and host cells to influence animal physiology and susceptibility to pathogens. Genomic methods have provided a broad framework for understanding how alterations in microbial communities are associated with host physiology and infection, but the biochemical mechanisms of specific intestinal bacterial species are only emerging. In this review, we focus on recent studies that have characterized the biochemical mechanisms by which intestinal bacteria interact with other bacteria and host pathways to restrict pathogen infection. Understanding the biochemical mechanisms of intestinal microbiota function should provide new opportunities for therapeutic development towards a variety of infectious diseases.

  • How Do Enzymes ‘Meet’ Nanoparticles and Nanomaterials?
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-13
    Ming Chen, Guangming Zeng, Piao Xu, Cui Lai, Lin Tang

    Enzymes are fundamental biological catalysts responsible for biological regulation and metabolism. The opportunity for enzymes to ‘meet’ nanoparticles and nanomaterials is rapidly increasing due to growing demands for applications in nanomaterial design, environmental monitoring, biochemical engineering, and biomedicine. Therefore, understanding the nature of nanomaterial–enzyme interactions is becoming important. Since 2014, enzymes have been used to modify, degrade, or make nanoparticles/nanomaterials, while numerous nanoparticles/nanomaterials have been used as materials for enzymatic immobilization and biosensors and as enzyme mimicry. Among the various nanoparticles and nanomaterials, metal nanoparticles and carbon nanomaterials have received extensive attention due to their fascinating properties. This review provides an overview about how enzymes meet nanoparticles and nanomaterials.

  • How Fast Is Protein–Ligand Association?
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-13
    Stefano Gianni, Per Jemth

    There is increasing interest in studying protein interactions and their role in cell biology using kinetics. However, there is confusion about the proper terminology in terms of the distinction between rates and rate constants. We recommend a more stringent use of the words speed, fast, slow, rate, and rate constant.

  • Emerging Structural Understanding of Amyloid Fibrils by Solid-State NMR
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-12
    Beat H. Meier, Roland Riek, Anja Böckmann

    Amyloid structures at atomic resolution have remained elusive mainly because of their extensive polymorphism and because their polymeric properties have hampered structural studies by classical approaches. Progress in sample preparation, as well as solid-state NMR methods, recently enabled the determination of high-resolution 3D structures of fibrils such as the amyloid-β fibril, which is involved in Alzheimer’s disease. Notably, the simultaneous but independent structure determination of Aβ1-42, a peptide that forms fibrillar deposits in the brain of Alzheimer patients, by two independent laboratories, which yielded virtually identical results, has highlighted how structures can be obtained that allow further functional investigation.

  • Stress-Activated Chaperones: A First Line of Defense
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-08
    Wilhelm Voth, Ursula Jakob

    Proteins are constantly challenged by environmental stress conditions that threaten their structure and function. Especially problematic are oxidative, acid, and severe heat stress which induce very rapid and widespread protein unfolding and generate conditions that make canonical chaperones and/or transcriptional responses inadequate to protect the proteome. We review here recent advances in identifying and characterizing stress-activated chaperones which are inactive under non-stress conditions but become potent chaperones under specific protein-unfolding stress conditions. We discuss the post-translational mechanisms by which these chaperones sense stress, and consider the role that intrinsic disorder plays in their regulation and function. We examine their physiological roles under both non-stress and stress conditions, their integration into the cellular proteostasis network, and their potential as novel therapeutic targets.

  • Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-09-01
    S. Branden Van Oss, Christine E. Cucinotta, Karen M. Arndt

    The conserved, multifunctional Polymerase-Associated Factor 1 complex (Paf1C) regulates all stages of the RNA polymerase (Pol) II transcription cycle. In this review, we examine a diverse set of recent studies from various organisms that build on foundational studies in budding yeast. These studies identify new roles for Paf1C in the control of gene expression and the regulation of chromatin structure. In exploring these advances, we find that various functions of Paf1C, such as the regulation of promoter-proximal pausing and development in higher eukaryotes, are complex and context dependent. As more becomes known about the role of Paf1C in human disease, interest in the molecular mechanisms underpinning Paf1C function will continue to increase.

  • There Is an Inclusion for That: Material Properties of Protein Granules Provide a Platform for Building Diverse Cellular Functions
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-08-29
    Daniel Kaganovich

    Proteins perform a staggering variety of functions in the cell. Traditionally, protein function was thought to be hard-wired into the folded structure and conformational dynamics of each protein molecule. Recent work describes a new mode of protein functionality driven by the collective behavior of many different proteins; most of which lack a defined structure. These proteins form clusters or granules in which unstructured polypeptides interact transiently. Nonspecific multivalent interactions drive the formation of phase-separated structures resembling aggregates. This type of functional aggregate granule can be thought of as a single supermolecular functional entity that derives function from its unique material properties. In this review we examine the emerging idea of protein granules as a new functional and structural unit of cellular organization.

  • In the Hunger Games, the Winner Takes Everything
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-08-28
    Franziska Püschel, Cristina Muñoz-Pinedo

    Entosis is an atypical form of cell death that occurs when a cell engulfs and kills another cell. A recent article by Overholtzer and colleagues indicates that glucose deprivation promotes entosis. AMP-activated protein kinase (AMPK) activation in the loser cells triggers their engulfment and elimination by winner cells, which endure starvation.

  • Good Ol’ Fat: Links between Lipid Signaling and Longevity
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-08-09
    Victor Bustos, Linda Partridge

    Aging is the single greatest risk factor for the development of disease. Understanding the biological molecules and mechanisms that modulate aging is therefore critical for the development of health-maximizing interventions for older people. The effect of fats on longevity has traditionally been disregarded as purely detrimental. However, new studies are starting to uncover the possible beneficial effects of lipids working as signaling molecules on health and longevity. These studies highlight the complex links between aging and lipid signaling. In this review we summarize accumulating evidence that points to changes in lipid metabolism, and in particular lipid signaling, as an underlying mechanism for healthy aging.

  • The Ribosome Holds the RNA Polymerase on Track in Bacteria
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-08-08
    Bruno P. Klaholz

    The central dogma of molecular biology comprises two fundamental mechanistic steps of gene expression (transcription and translation), which, in bacteria, are coupled. A recent study provides structural insights into a supercomplex between the RNA polymerase and the ribosome, thus highlighting the synergy between two key macromolecular machineries in the cell.

  • How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-08-04
    Kliment A. Verba, David A. Agard

    The Hsp90/Cdc37 chaperone system interacts with and supports 60% of the human kinome. Not only are Hsp90 and Cdc37 generally required for initial folding, but many kinases rely on the Hsp90/Cdc37 throughout their lifetimes. A large fraction of these ‘client’ kinases are key oncoproteins, and their interactions with the Hsp90/Cdc37 machinery are crucial for both their normal and malignant activity. Recently, advances in single-particle cryo-electron microscopy (cryoEM) and biochemical strategies have provided the first key molecular insights into kinase–chaperone interactions. The surprising results suggest a re-evaluation of the role of chaperones in the kinase lifecycle, and suggest that such interactions potentially allow kinases to more rapidly respond to key signals while simultaneously protecting unstable kinases from degradation and suppressing unwanted basal activity.

  • d-Tyrosyl-tRNA Deacylase: A New Function
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-07-29
    Richard Calendar

    d-Aminoacyl-tRNA deacylase (DTD) hydrolyzes d-amino acids mistakenly attached to tRNAs and, thus, has been implicated in perpetuating protein homochirality. Fifty years after the discovery of DTD, it has now been shown that its function extends beyond ‘chiral proofreading’ because it also eliminates glycine that has been erroneously coupled to tRNAAla.

  • A Process of Resection-Dependent Nonhomologous End Joining Involving the Goddess Artemis
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-07-21
    Markus Löbrich, Penny Jeggo

    DNA double-strand breaks (DSBs) are a hazardous form of damage that can potentially cause cell death or genomic rearrangements. In mammalian G1- and G2-phase cells, DSBs are repaired with two-component kinetics. In both phases, a fast process uses canonical nonhomologous end joining (c-NHEJ) to repair the majority of DSBs. In G2, slow repair occurs by homologous recombination. The slow repair process in G1 also involves c-NHEJ proteins but additionally requires the nuclease Artemis and DNA end resection. Here, we consider the nature of slow DSB repair in G1 and evaluate factors determining whether DSBs are repaired with fast or slow kinetics. We consider limitations in our current knowledge and present a speculative model for Artemis-dependent c-NHEJ and the environment underlying its usage.

  • Phosphatidylserine Is the Signal for TAM Receptors and Their Ligands
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-07-19
    Greg Lemke

    Nature repeatedly repurposes, in that molecules that serve as metabolites, energy depots, or polymer subunits are at the same time used to deliver signals within and between cells. The preeminent example of this repurposing is ATP, which functions as a building block for nucleic acids, an energy source for enzymatic reactions, a phosphate donor to regulate intracellular signaling, and a neurotransmitter to control the activity of neurons. A series of recent studies now consolidates the view that phosphatidylserine (PtdSer), a common phospholipid constituent of membrane bilayers, is similarly repurposed for use as a signal between cells and that the ligands and receptors of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases (RTKs) are prominent transducers of this signal.

  • A Bright Future for Serial Femtosecond Crystallography with XFELs
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-07-18
    Linda C. Johansson, Benjamin Stauch, Andrii Ishchenko, Vadim Cherezov

    X-ray free electron lasers (XFELs) have the potential to revolutionize macromolecular structural biology due to the unique combination of spatial coherence, extreme peak brilliance, and short duration of X-ray pulses. A recently emerged serial femtosecond (fs) crystallography (SFX) approach using XFEL radiation overcomes some of the biggest hurdles of traditional crystallography related to radiation damage through the diffraction-before-destruction principle. Intense fs XFEL pulses enable high-resolution room-temperature structure determination of difficult-to-crystallize biological macromolecules, while simultaneously opening a new era of time-resolved structural studies. Here, we review the latest developments in instrumentation, sample delivery, data analysis, crystallization methods, and applications of SFX to important biological questions, and conclude with brief insights into the bright future of structural biology using XFELs.

  • Shaping and Reshaping Transcriptome Plasticity during Evolution
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-07-14
    Shobbir Hussain

    Transcriptome plasticity, usually associated with alternative isoform generation, is recognised as a key mechanism driving proteomic diversity and biological complexity. Recent findings of Liscovitch-Brauer et al. and Ma et al. suggest that RNA base modifications are an additional central mode of transcriptome malleability that have the potential to determine evolutionary outcomes.

  • Biphasic Modeling of Mitochondrial Metabolism Dysregulation during Aging
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-06-29
    Darren J. Baker, Shahaf Peleg

    Organismal aging is classically viewed as a gradual decline of cellular functions and a systemic deterioration of tissues that leads to an increased mortality rate in older individuals. According to the prevailing theory, aging is accompanied by a continuous and progressive decline in mitochondrial metabolic activity in cells. However, the most robust approaches to extending healthy lifespan are frequently linked with reduced energy intake or with lowering of mitochondrial activity. While these observations appear contradictory, recent work and technological advances demonstrate that metabolic deregulation during aging is potentially biphasic. In this Opinion we propose a novel framework where middle-age is accompanied by increased mitochondrial activity that subsequently declines at advanced ages.

  • Cytosolic Proteostasis Networks of the Mitochondrial Stress Response
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-06-01
    Davide D’Amico, Vincenzo Sorrentino, Johan Auwerx

    Mitochondrial stress requires timely intervention to prevent mitochondrial and cellular dysfunction. Re-establishing the correct protein homeostasis is crucial for coping with mitochondrial stress and maintaining cellular homeostasis. The best-characterized adaptive pathways for mitochondrial stress involve a signal originating from stressed mitochondria that triggers a nuclear response. However, recent findings have shown that mitochondrial stress also affects a complex network of protein homeostasis pathways in the cytosol. We review how mitochondrial dysregulation affects cytosolic proteostasis by regulating the quantity and quality of protein synthesis, protein stability, and protein degradation, leading to an integrated regulation of cellular metabolism and proliferation. This mitochondria to cytosol network extends the current model of the mitochondrial stress response, with potential applications in the treatment of mitochondrial disease.

  • Bacterial Inclusion Bodies: Discovering Their Better Half
    Trends Biochem. Sci. (IF 16.63) Pub Date : 2017-02-27
    Ursula Rinas, Elena Garcia-Fruitós, José Luis Corchero, Esther Vázquez, Joaquin Seras-Franzoso, Antonio Villaverde

    Bacterial inclusion bodies (IBs) are functional, non-toxic amyloids occurring in recombinant bacteria showing analogies with secretory granules of the mammalian endocrine system. The scientific interest in these mesoscale protein aggregates has been historically masked by their status as a hurdle in recombinant protein production. However, progressive understanding of how the cell handles the quality of recombinant polypeptides and the main features of their intriguing molecular organization has stimulated the interest in inclusion bodies and spurred their use in diverse technological fields. The engineering and tailoring of IBs as functional protein particles for materials science and biomedicine is a good example of how formerly undesired bacterial byproducts can be rediscovered as promising functional materials for a broad spectrum of applications.

Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
化学 • 材料 期刊列表