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  • Molecular Mechanisms of Natural Rubber Biosynthesis.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Satoshi Yamashita,Seiji Takahashi

    Natural rubber (NR), principally comprising cis-1,4-polyisoprene, is an industrially important natural hydrocarbon polymer because of its unique physical properties, which render it suitable for manufacturing items such as tires. Presently, industrial NR production depends solely on latex obtained from the Pará rubber tree, Hevea brasiliensis. In latex, NR is enclosed in rubber particles, which are

    更新日期:2020-06-23
  • Current Understanding of the Mechanism of Water Oxidation in Photosystem II and Its Relation to XFEL Data.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Nicholas Cox,Dimitrios A Pantazis,Wolfgang Lubitz

    The investigation of water oxidation in photosynthesis has remained a central topic in biochemical research for the last few decades due to the importance of this catalytic process for technological applications. Significant progress has been made following the 2011 report of a high-resolution X-ray crystallographic structure resolving the site of catalysis, a protein-bound Mn4CaOx complex, which passes

    更新日期:2020-06-23
  • Mucins and the Microbiome.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Gunnar C Hansson

    Generating the barriers that protect our inner surfaces from bacteria and other challenges requires large glycoproteins called mucins. These come in two types, gel-forming and transmembrane, all characterized by large, highly O-glycosylated mucin domains that are diversely decorated by Golgi glycosyltransferases to become extended rodlike structures. The general functions of mucins on internal epithelial

    更新日期:2020-06-23
  • Biosynthesis and Export of Bacterial Glycolipids.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Christopher A Caffalette,Jeremi Kuklewicz,Nicholas Spellmon,Jochen Zimmer

    Complex carbohydrates are essential for many biological processes, from protein quality control to cell recognition, energy storage, and cell wall formation. Many of these processes are performed in topologically extracellular compartments or on the cell surface; hence, diverse secretion systems evolved to transport the hydrophilic molecules to their sites of action. Polyprenyl lipids serve as ubiquitous

    更新日期:2020-06-23
  • HLAs, TCRs, and KIRs, a Triumvirate of Human Cell-Mediated Immunity.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Zakia Djaoud,Peter Parham

    In all human cells, human leukocyte antigen (HLA) class I glycoproteins assemble with a peptide and take it to the cell surface for surveillance by lymphocytes. These include natural killer (NK) cells and γδ T cells of innate immunity and αβ T cells of adaptive immunity. In healthy cells, the presented peptides derive from human proteins, to which lymphocytes are tolerant. In pathogen-infected cells

    更新日期:2020-06-23
  • Zona Pellucida Proteins, Fibrils, and Matrix.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Eveline S Litscher,Paul M Wassarman

    The zona pellucida (ZP) is an extracellular matrix that surrounds all mammalian oocytes, eggs, and early embryos and plays vital roles during oogenesis, fertilization, and preimplantation development. The ZP is composed of three or four glycosylated proteins, ZP1–4, that are synthesized, processed, secreted, and assembled into long, cross-linked fibrils by growing oocytes. ZP proteins have an immunoglobulin-like

    更新日期:2020-06-23
  • The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Darshan V Trivedi,Suman Nag,Annamma Spudich,Kathleen M Ruppel,James A Spudich

    Myosins are among the most fascinating enzymes in biology. As extremely allosteric chemomechanical molecular machines, myosins are involved in myriad pivotal cellular functions and are frequently sites of mutations leading to disease phenotypes. Human β-cardiac myosin has proved to be an excellent target for small-molecule therapeutics for heart muscle diseases, and, as we describe here, other myosin

    更新日期:2020-06-23
  • Double the Fun, Double the Trouble: Paralogs and Homologs Functioning in the Endoplasmic Reticulum.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Emma J Fenech,Shifra Ben-Dor,Maya Schuldiner

    The evolution of eukaryotic genomes has been propelled by a series of gene duplication events, leading to an expansion in new functions and pathways. While duplicate genes may retain some functional redundancy, it is clear that to survive selection they cannot simply serve as a backup but rather must acquire distinct functions required for cellular processes to work accurately and efficiently. Understanding

    更新日期:2020-06-23
  • Structural and Mechanistic Principles of ABC Transporters.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Christoph Thomas,Robert Tampé

    ATP-binding cassette (ABC) transporters constitute one of the largest and most ancient protein superfamilies found in all living organisms. They function as molecular machines by coupling ATP binding, hydrolysis, and phosphate release to translocation of diverse substrates across membranes. The substrates range from vitamins, steroids, lipids, and ions to peptides, proteins, polysaccharides, and xenobiotics

    更新日期:2020-06-23
  • Structure and Mechanism of P-Type ATPase Ion Pumps.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Mateusz Dyla,Magnus Kjærgaard,Hanne Poulsen,Poul Nissen

    P-type ATPases are found in all kingdoms of life and constitute a wide range of cation transporters, primarily for H+, Na+, K+, Ca2+, and transition metal ions such as Cu(I), Zn(II), and Cd(II). They have been studied through a wide range of techniques, and research has gained very significant insight on their transport mechanism and regulation. Here, we review the structure, function, and dynamics

    更新日期:2020-06-23
  • Quantifying Target Occupancy of Small Molecules Within Living Cells.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    M B Robers,R Friedman-Ohana,K V M Huber,L Kilpatrick,J D Vasta,B-T Berger,C Chaudhry,S Hill,S Müller,S Knapp,K V Wood

    The binding affinity and kinetics of target engagement are fundamental to establishing structure–activity relationships (SARs) for prospective therapeutic agents. Enhancing these binding parameters for operative targets, while minimizing binding to off-target sites, can translate to improved drug efficacy and a widened therapeutic window. Compound activity is typically assessed through modulation of

    更新日期:2020-06-23
  • Chemical Biology Framework to Illuminate Proteostasis.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Rebecca M Sebastian,Matthew D Shoulders

    Protein folding in the cell is mediated by an extensive network of >1,000 chaperones, quality control factors, and trafficking mechanisms collectively termed the proteostasis network. While the components and organization of this network are generally well established, our understanding of how protein-folding problems are identified, how the network components integrate to successfully address challenges

    更新日期:2020-06-23
  • Mitochondrial Proteases: Multifaceted Regulators of Mitochondrial Plasticity.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Soni Deshwal,Kai Uwe Fiedler,Thomas Langer

    Mitochondria are essential metabolic hubs that dynamically adapt to physiological demands. More than 40 proteases residing in different compartments of mitochondria, termed mitoproteases, preserve mitochondrial proteostasis and are emerging as central regulators of mitochondrial plasticity. These multifaceted enzymes limit the accumulation of short-lived, regulatory proteins within mitochondria, modulate

    更新日期:2020-06-23
  • Mechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Roland Lill,Sven-A Freibert

    Mitochondria are essential in most eukaryotes and are involved in numerous biological functions including ATP production, cofactor biosyntheses, apoptosis, lipid synthesis, and steroid metabolism. Work over the past two decades has uncovered the biogenesis of cellular iron-sulfur (Fe/S) proteins as the essential and minimal function of mitochondria. This process is catalyzed by the bacteria-derived

    更新日期:2020-06-23
  • Single-Molecule Studies of Protein Folding with Optical Tweezers.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Carlos Bustamante,Lisa Alexander,Kevin Maciuba,Christian M Kaiser

    Manipulation of individual molecules with optical tweezers provides a powerful means of interrogating the structure and folding of proteins. Mechanical force is not only a relevant quantity in cellular protein folding and function, but also a convenient parameter for biophysical folding studies. Optical tweezers offer precise control in the force range relevant for protein folding and unfolding, from

    更新日期:2020-06-23
  • Detection and Degradation of Stalled Nascent Chains via Ribosome-Associated Quality Control.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Cole S Sitron,Onn Brandman

    Stalled protein synthesis produces defective nascent chains that can harm cells. In response, cells degrade these nascent chains via a process called ribosome-associated quality control (RQC). Here, we review the irregularities in the translation process that cause ribosomes to stall as well as how cells use RQC to detect stalled ribosomes, ubiquitylate their tethered nascent chains, and deliver the

    更新日期:2020-06-23
  • How Does the Ribosome Fold the Proteome?
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Anaïs M E Cassaignau,Lisa D Cabrita,John Christodoulou

    Folding of polypeptides begins during their synthesis on ribosomes. This process has evolved as a means for the cell to maintain proteostasis, by mitigating the risk of protein misfolding and aggregation. The capacity to now depict this cellular feat at increasingly higher resolution is providing insight into the mechanistic determinants that promote successful folding. Emerging from these studies

    更新日期:2020-06-23
  • RNA Splicing by the Spliceosome.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Max E Wilkinson,Clément Charenton,Kiyoshi Nagai

    The spliceosome removes introns from messenger RNA precursors (pre-mRNA). Decades of biochemistry and genetics combined with recent structural studies of the spliceosome have produced a detailed view of the mechanism of splicing. In this review, we aim to make this mechanism understandable and provide several videos of the spliceosome in action to illustrate the intricate choreography of splicing.

    更新日期:2020-06-23
  • How Is Precursor Messenger RNA Spliced by the Spliceosome?
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Ruixue Wan,Rui Bai,Xiechao Zhan,Yigong Shi

    Splicing of the precursor messenger RNA, involving intron removal and exon ligation, is mediated by the spliceosome. Together with biochemical and genetic investigations of the past four decades, structural studies of the intact spliceosome at atomic resolution since 2015 have led to mechanistic delineation of RNA splicing with remarkable insights. The spliceosome is proven to be a protein-orchestrated

    更新日期:2020-06-23
  • Anti-CRISPRs: Protein Inhibitors of CRISPR-Cas Systems.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Alan R Davidson,Wang-Ting Lu,Sabrina Y Stanley,Jingrui Wang,Marios Mejdani,Chantel N Trost,Brian T Hicks,Jooyoung Lee,Erik J Sontheimer

    Clustered regularly interspaced short palindromic repeats (CRISPR) together with their accompanying cas (CRISPR-associated) genes are found frequently in bacteria and archaea, serving to defend against invading foreign DNA, such as viral genomes. CRISPR-Cas systems provide a uniquely powerful defense because they can adapt to newly encountered genomes. The adaptive ability of these systems has been

    更新日期:2020-06-23
  • Long Noncoding RNAs: Molecular Modalities to Organismal Functions.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    John L Rinn,Howard Y Chang

    We have known for decades that long noncoding RNAs (lncRNAs) can play essential functions across most forms of life. The maintenance of chromosome length requires an lncRNA (e.g., hTERC) and two lncRNAs in the ribosome that are required for protein synthesis. Thus, lncRNAs can represent powerful RNA machines. More recently, it has become clear that mammalian genomes encode thousands more lncRNAs. Thus

    更新日期:2020-06-23
  • Molecular Mechanisms of Facultative Heterochromatin Formation: An X-Chromosome Perspective.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Jan J Żylicz,Edith Heard

    Facultative heterochromatin (fHC) concerns the developmentally regulated heterochromatinization of different regions of the genome and, in the case of the mammalian X chromosome and imprinted loci, of only one allele of a homologous pair. The formation of fHC participates in the timely repression of genes, by resisting strong trans activators. In this review, we discuss the molecular mechanisms underlying

    更新日期:2020-06-23
  • Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Mitzi I Kuroda,Hyuckjoon Kang,Sandip De,Judith A Kassis

    Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of the genome by chromatin proteins, histone modifications, and differential compaction is largely sufficient to reveal the locations of genes and their differential activity states. The Polycomb Group (PcG) and Trithorax Group (TrxG) proteins are the central

    更新日期:2020-06-23
  • Evaluating Enhancer Function and Transcription.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Andrew Field,Karen Adelman

    Cell-type- and condition-specific profiles of gene expression require coordination between protein-coding gene promoters and cis-regulatory sequences called enhancers. Enhancers can stimulate gene activity at great genomic distances from their targets, raising questions about how enhancers communicate with specific gene promoters and what molecular mechanisms underlie enhancer function. Characterization

    更新日期:2020-06-23
  • Transcription in Living Cells: Molecular Mechanisms of Bursting.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Joseph Rodriguez,Daniel R Larson

    Transcription in several organisms from certain bacteria to humans has been observed to be stochastic in nature: toggling between active and inactive states. Periods of active nascent RNA synthesis known as bursts represent individual gene activation events in which multiple polymerases are initiated. Therefore, bursting is the single locus illustration of both gene activation and repression. Although

    更新日期:2020-06-23
  • Imaging of DNA and RNA in Living Eukaryotic Cells to Reveal Spatiotemporal Dynamics of Gene Expression.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Hanae Sato,Sulagna Das,Robert H Singer,Maria Vera

    This review focuses on imaging DNA and single RNA molecules in living cells to define eukaryotic functional organization and dynamic processes. The latest advances in technologies to visualize individual DNA loci and RNAs in real time are discussed. Single-molecule fluorescence microscopy provides the spatial and temporal resolution to reveal mechanisms regulating fundamental cell functions. Novel

    更新日期:2020-06-23
  • Role of Mammalian DNA Methyltransferases in Development.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Zhiyuan Chen,Yi Zhang

    DNA methylation at the 5-position of cytosine (5mC) plays vital roles in mammalian development. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), and the two DNMT families, DNMT3 and DNMT1, are responsible for methylation establishment and maintenance, respectively. Since their discovery, biochemical and structural studies have revealed the key mechanisms underlying how DNMTs catalyze

    更新日期:2020-06-23
  • Checkpoint Responses to DNA Double-Strand Breaks.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    David P Waterman,James E Haber,Marcus B Smolka

    Cells confront DNA damage in every cell cycle. Among the most deleterious types of DNA damage are DNA double-strand breaks (DSBs), which can cause cell lethality if unrepaired or cancers if improperly repaired. In response to DNA DSBs, cells activate a complex DNA damage checkpoint (DDC) response that arrests the cell cycle, reprograms gene expression, and mobilizes DNA repair factors to prevent the

    更新日期:2020-06-23
  • Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Brandon L Greene,Gyunghoon Kang,Chang Cui,Marina Bennati,Daniel G Nocera,Catherine L Drennan,JoAnne Stubbe

    Ribonucleotide reductases (RNRs) catalyze the de novo conversion of nucleotides to deoxynucleotides in all organisms, controlling their relative ratios and abundance. In doing so, they play an important role in fidelity of DNA replication and repair. RNRs’ central role in nucleic acid metabolism has resulted in five therapeutics that inhibit human RNRs. In this review, we discuss the structural, dynamic

    更新日期:2020-06-23
  • Standing on the Shoulders of Viruses.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Ari Helenius

    My coworkers and I have used animal viruses and their interaction with host cells to investigate cellular processes difficult to study by other means. This approach has allowed us to branch out in many directions, including membrane protein characterization, endocytosis, secretion, protein folding, quality control, and glycobiology. At the same time, our aim has been to employ cell biological approaches

    更新日期:2020-06-23
  • Christopher Dobson, 1949-2019: Mentor, Friend, Scientist Extraordinaire.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Carol V Robinson

    It is impossible to do justice in one review article to a researcher of the stature of Christopher Dobson. His career spanned almost five decades, resulting in more than 870 publications and a legacy that will continue to influence the lives of many for decades to come. In this review, I have attempted to capture Chris's major contributions: his early work, dedicated to understanding protein-folding

    更新日期:2020-06-23
  • Synthetic Genomes.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2020-06-22
    Weimin Zhang,Leslie A Mitchell,Joel S Bader,Jef D Boeke

    DNA synthesis technology has progressed to the point that it is now practical to synthesize entire genomes. Quite a variety of methods have been developed, first to synthesize single genes but ultimately to massively edit or write from scratch entire genomes. Synthetic genomes can essentially be clones of native sequences, but this approach does not teach us much new biology. The ability to endow genomes

    更新日期:2020-06-22
  • Botulinum and Tetanus Neurotoxins.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Min Dong,Geoffrey Masuyer,Pål Stenmark

    Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct

    更新日期:2020-04-21
  • Propagation of Protein Aggregation in Neurodegenerative Diseases.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Jaime Vaquer-Alicea,Marc I Diamond

    Most common neurodegenerative diseases feature deposition of protein amyloids and degeneration of brain networks. Amyloids are ordered protein assemblies that can act as templates for their own replication through monomer addition. Evidence suggests that this characteristic may underlie the progression of pathology in neurodegenerative diseases. Many different amyloid proteins, including Aβ, tau, and

    更新日期:2020-04-21
  • The Structure of the Nuclear Pore Complex (An Update).
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Daniel H Lin,André Hoelz

    The nuclear pore complex (NPC) serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Owing to its size and complexity (∼1,000 protein subunits, ∼110 MDa in humans), the NPC has remained one of the foremost challenges for structure determination. Structural studies have now provided atomic-resolution crystal structures of most nucleoporins. The acquisition of these structures

    更新日期:2020-04-21
  • Mechanism and Regulation of Centriole and Cilium Biogenesis.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    David K Breslow,Andrew J Holland

    The centriole is an ancient microtubule-based organelle with a conserved nine-fold symmetry. Centrioles form the core of centrosomes, which organize the interphase microtubule cytoskeleton of most animal cells and form the poles of the mitotic spindle. Centrioles can also be modified to form basal bodies, which template the formation of cilia and play central roles in cellular signaling, fluid movement

    更新日期:2020-04-21
  • Molecular Mechanism of Cytokinesis.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Thomas D Pollard,Ben O'Shaughnessy

    Division of amoebas, fungi, and animal cells into two daughter cells at the end of the cell cycle depends on a common set of ancient proteins, principally actin filaments and myosin-II motors. Anillin, formins, IQGAPs, and many other proteins regulate the assembly of the actin filaments into a contractile ring positioned between the daughter nuclei by different mechanisms in fungi and animal cells

    更新日期:2020-04-21
  • Single-Molecule Kinetics in Living Cells.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Johan Elf,Irmeli Barkefors

    In the past decades, advances in microscopy have made it possible to study the dynamics of individual biomolecules in vitro and resolve intramolecular kinetics that would otherwise be hidden in ensemble averages. More recently, single-molecule methods have been used to image, localize, and track individually labeled macromolecules in the cytoplasm of living cells, allowing investigations of intermolecular

    更新日期:2020-04-21
  • Small-Molecule-Based Fluorescent Sensors for Selective Detection of Reactive Oxygen Species in Biological Systems.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Xiaoyu Bai,Kenneth King-Hei Ng,Jun Jacob Hu,Sen Ye,Dan Yang

    Reactive oxygen species (ROS) encompass a collection of intricately linked chemical entities characterized by individually distinct physicochemical properties and biological reactivities. Although excessive ROS generation is well known to underpin disease development, it has become increasingly evident that ROS also play central roles in redox regulation and normal physiology. A major challenge in

    更新日期:2020-04-21
  • The Hippo Pathway: Biology and Pathophysiology.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Shenghong Ma,Zhipeng Meng,Rui Chen,Kun-Liang Guan

    The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size control, and regeneration. The core of the Hippo pathway in mammals consists of a kinase cascade, MST1/2 and LATS1/2, as well as downstream effectors

    更新日期:2020-04-21
  • ECF-Type ATP-Binding Cassette Transporters.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    S Rempel,W K Stanek,D J Slotboom

    Energy-coupling factor (ECF)-type ATP-binding cassette (ABC) transporters catalyze membrane transport of micronutrients in prokaryotes. Crystal structures and biochemical characterization have revealed that ECF transporters are mechanistically distinct from other ABC transport systems. Notably, ECF transporters make use of small integral membrane subunits (S-components) that are predicted to topple

    更新日期:2020-04-21
  • Structure and Mechanisms of F-Type ATP Synthases.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Werner Kühlbrandt

    F1Fo ATP synthases produce most of the ATP in the cell. F-type ATP synthases have been investigated for more than 50 years, but a full understanding of their molecular mechanisms has become possible only with the recent structures of complete, functionally competent complexes determined by electron cryo-microscopy (cryo-EM). High-resolution cryo-EM structures offer a wealth of unexpected new insights

    更新日期:2020-04-21
  • Exosomes.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    D Michiel Pegtel,Stephen J Gould

    Exosomes are small, single-membrane, secreted organelles of ∼30 to ∼200 nm in diameter that have the same topology as the cell and are enriched in selected proteins, lipids, nucleic acids, and glycoconjugates. Exosomes contain an array of membrane-associated, high-order oligomeric protein complexes, display pronounced molecular heterogeneity, and are created by budding at both plasma and endosome membranes

    更新日期:2020-04-21
  • Lysosomal Glycosphingolipid Storage Diseases.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Bernadette Breiden,Konrad Sandhoff

    Glycosphingolipids are cell-type-specific components of the outer leaflet of mammalian plasma membranes. Gangliosides, sialic acid-containing glycosphingolipids, are especially enriched on neuronal surfaces. As amphi-philic molecules, they comprise a hydrophilic oligosaccharide chain attached to a hydrophobic membrane anchor, ceramide. Whereas glycosphingolipid formation is catalyzed by membrane-bound

    更新日期:2020-04-21
  • Glycoengineering of Antibodies for Modulating Functions.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Lai-Xi Wang,Xin Tong,Chao Li,John P Giddens,Tiezheng Li

    Antibodies are immunoglobulins that play essential roles in immune systems. All antibodies are glycoproteins that carry at least one or more conserved N-linked oligosaccharides (N-glycans) at the Fc domain. Many studies have demonstrated that both the presence and fine structures of the attached glycans can exert a profound impact on the biological functions and therapeutic efficacy of antibodies.

    更新日期:2020-04-21
  • Soluble Methane Monooxygenase.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Rahul Banerjee,Jason C Jones,John D Lipscomb

    Aerobic life is possible because the molecular structure of oxygen (O2) makes direct reaction with most organic materials at ambient temperatures an exceptionally slow process. Of course, these reactions are inherently very favorable, and they occur rapidly with the release of a great deal of energy at high temperature. Nature has been able to tap this sequestered reservoir of energy with great spatial

    更新日期:2020-04-21
  • Horizontal Cell Biology: Monitoring Global Changes of Protein Interaction States with the Proteome-Wide Cellular Thermal Shift Assay (CETSA).
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Lingyun Dai,Nayana Prabhu,Liang Ying Yu,Smaranda Bacanu,Anderson Daniel Ramos,Pär Nordlund

    The cellular thermal shift assay (CETSA) is a biophysical technique allowing direct studies of ligand binding to proteins in cells and tissues. The proteome-wide implementation of CETSA with mass spectrometry detection (MS-CETSA) has now been successfully applied to discover targets for orphan clinical drugs and hits from phenotypic screens, to identify off-targets, and to explain poly-pharmacology

    更新日期:2020-04-21
  • Lysine-Targeted Inhibitors and Chemoproteomic Probes.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Adolfo Cuesta,Jack Taunton

    Covalent inhibitors are widely used in drug discovery and chemical biology. Although covalent inhibitors are frequently designed to react with noncatalytic cysteines, many ligand binding sites lack an accessible cysteine. Here, we review recent advances in the chemical biology of lysine-targeted covalent inhibitors and chemoproteomic probes. By analyzing crystal structures of proteins bound to common

    更新日期:2020-04-21
  • Mechanisms of Cotranslational Maturation of Newly Synthesized Proteins.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Günter Kramer,Ayala Shiber,Bernd Bukau

    The timely production of functional proteins is of critical importance for the biological activity of cells. To reach the functional state, newly synthesized polypeptides have to become enzymatically processed, folded, and assembled into oligomeric complexes and, for noncytosolic proteins, translocated across membranes. Key activities of these processes occur cotranslationally, assisted by a network

    更新日期:2020-04-21
  • The Organizing Principles of Eukaryotic Ribosome Recruitment.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Jerry Pelletier,Nahum Sonenberg

    The stage at which ribosomes are recruited to messenger RNAs (mRNAs) is an elaborate and highly regulated phase of protein synthesis. Upon completion of this step, a ribosome is positioned at an appropriate initiation codon and primed to synthesize the encoded polypeptide product. In most circumstances, this step commits the ribosome to translate the mRNA. We summarize the knowledge regarding the initiation

    更新日期:2020-04-21
  • Eukaryotic Ribosome Assembly.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Jochen Baßler,Ed Hurt

    Ribosomes, which synthesize the proteins of a cell, comprise ribosomal RNA and ribosomal proteins, which coassemble hierarchically during a process termed ribosome biogenesis. Historically, biochemical and molecular biology approaches have revealed how preribosomal particles form and mature in consecutive steps, starting in the nucleolus and terminating after nuclear export into the cytoplasm. However

    更新日期:2020-04-21
  • Cancer Treatment in the Genomic Era.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Gary J Doherty,Michele Petruzzelli,Emma Beddowes,Saif S Ahmad,Carlos Caldas,Richard J Gilbertson

    The complexity of human cancer underlies its devastating clinical consequences. Drugs designed to target the genetic alterations that drive cancer have improved the outcome for many patients, but not the majority of them. Here, we review the genomic landscape of cancer, how genomic data can provide much more than a sum of its parts, and the approaches developed to identify and validate genomic alterations

    更新日期:2020-04-21
  • The BRCA Tumor Suppressor Network in Chromosome Damage Repair by Homologous Recombination.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Weixing Zhao,Claudia Wiese,Youngho Kwon,Robert Hromas,Patrick Sung

    Mutations in the BRCA1 and BRCA2 genes predispose afflicted individuals to breast, ovarian, and other cancers. The BRCA-encoded products form complexes with other tumor suppressor proteins and with the recombinase enzyme RAD51 to mediate chromosome damage repair by homologous recombination and also to protect stressed DNA replication forks against spurious nucleolytic attrition. Understanding how the

    更新日期:2020-04-21
  • Evaluating and Enhancing Target Specificity of Gene-Editing Nucleases and Deaminases.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Daesik Kim,Kevin Luk,Scot A Wolfe,Jin-Soo Kim

    Programmable nucleases and deaminases, which include zinc-finger nucleases, transcription activator-like effector nucleases, CRISPR RNA-guided nucleases, and RNA-guided base editors, are now widely employed for the targeted modification of genomes in cells and organisms. These gene-editing tools hold tremendous promise for therapeutic applications. Importantly, these nucleases and deaminases may display

    更新日期:2020-04-21
  • Redox Chemistry in the Genome: Emergence of the [4Fe4S] Cofactor in Repair and Replication.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Jacqueline K Barton,Rebekah M B Silva,Elizabeth O'Brien

    Many DNA-processing enzymes have been shown to contain a [4Fe4S] cluster, a common redox cofactor in biology. Using DNA electrochemistry, we find that binding of the DNA polyanion promotes a negative shift in [4Fe4S] cluster potential, which corresponds thermodynamically to a ∼500-fold increase in DNA-binding affinity for the oxidized [4Fe4S]3+ cluster versus the reduced [4Fe4S]2+ cluster. This redox

    更新日期:2020-04-21
  • Eukaryotic Base Excision Repair: New Approaches Shine Light on Mechanism.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    William A Beard,Julie K Horton,Rajendra Prasad,Samuel H Wilson

    Genomic DNA is susceptible to endogenous and environmental stresses that modify DNA structure and its coding potential. Correspondingly, cells have evolved intricate DNA repair systems to deter changes to their genetic material. Base excision DNA repair involves a number of enzymes and protein cofactors that hasten repair of damaged DNA bases. Recent advances have identified macromolecular complexes

    更新日期:2020-04-21
  • Integrative Structure Modeling: Overview and Assessment.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Merav Braitbard,Dina Schneidman-Duhovny,Nir Kalisman

    Integrative structure modeling computationally combines data from multiple sources of information with the aim of obtaining structural insights that are not revealed by any single approach alone. In the first part of this review, we survey the commonly used sources of structural information and the computational aspects of model building. Throughout the past decade, integrative modeling was applied

    更新日期:2020-04-21
  • Membrane Protein-Lipid Interactions Probed Using Mass Spectrometry.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Jani Reddy Bolla,Mark T Agasid,Shahid Mehmood,Carol V Robinson

    Membrane proteins that exist in lipid bilayers are not isolated molecular entities. The lipid molecules that surround them play crucial roles in maintaining their full structural and functional integrity. Research directed at investigating these critical lipid-protein interactions is developing rapidly. Advancements in both instrumentation and software, as well as in key biophysical and biochemical

    更新日期:2020-04-21
  • Bacteriorhodopsin: Structural Insights Revealed Using X-Ray Lasers and Synchrotron Radiation.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Cecilia Wickstrand,Przemyslaw Nogly,Eriko Nango,So Iwata,Jörg Standfuss,Richard Neutze

    Directional transport of protons across an energy transducing membrane-proton pumping-is ubiquitous in biology. Bacteriorhodopsin (bR) is a light-driven proton pump that is activated by a buried all-trans retinal chromophore being photoisomerized to a 13-cis conformation. The mechanism by which photoisomerization initiates directional proton transport against a proton concentration gradient has been

    更新日期:2020-04-21
  • X-Ray Free-Electron Lasers for the Structure and Dynamics of Macromolecules.
    Annu. Rev. Biochem. (IF 25.787) Pub Date : 2019-06-20
    Henry N Chapman

    X-ray free-electron lasers provide femtosecond-duration pulses of hard X-rays with a peak brightness approximately one billion times greater than is available at synchrotron radiation facilities. One motivation for the development of such X-ray sources was the proposal to obtain structures of macromolecules, macromolecular complexes, and virus particles, without the need for crystallization, through

    更新日期:2020-04-21
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