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    2004 results match your criteria Annual Review of Biochemistry [Journal]

    1 OF 41

    Along the Central Dogma-Controlling Gene Expression with Small Molecules.
    Annu Rev Biochem 2018 May 4. Epub 2018 May 4.
    Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Saitama 351-0198, Japan; email:
    The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. Read More

    Ancient Biomolecules and Evolutionary Inference.
    Annu Rev Biochem 2018 Apr 25. Epub 2018 Apr 25.
    Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark; email: ,
    Over the last decade, studies of ancient biomolecules-particularly ancient DNA, proteins, and lipids-have revolutionized our understanding of evolutionary history. Though initially fraught with many challenges, the field now stands on firm foundations. Researchers now successfully retrieve nucleotide and amino acid sequences, as well as lipid signatures, from progressively older samples, originating from geographic areas and depositional environments that, until recently, were regarded as hostile to long-term preservation of biomolecules. Read More

    The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.
    Annu Rev Biochem 2018 Apr 25. Epub 2018 Apr 25.
    Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA; email: ,
    Genomic instability in disease and its fidelity in health depend on the DNA damage response (DDR), regulated in part from the complex of meiotic recombination 11 homolog 1 (MRE11), ATP-binding cassette-ATPase (RAD50), and phosphopeptide-binding Nijmegen breakage syndrome protein 1 (NBS1). The MRE11-RAD50-NBS1 (MRN) complex forms a multifunctional DDR machine. Within its network assemblies, MRN is the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection. Read More

    Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs.
    Annu Rev Biochem 2018 Apr 18. Epub 2018 Apr 18.
    Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiberg im Breisgau, Germany; email:
    X chromosome regulation represents a prime example of an epigenetic phenomenon where coordinated regulation of a whole chromosome is required. In flies, this is achieved by transcriptional upregulation of X chromosomal genes in males to equalize the gene dosage differences in females. Chromatin-bound proteins and long noncoding RNAs (lncRNAs) constituting a ribonucleoprotein complex known as the male-specific lethal (MSL) complex or the dosage compensation complex mediate this process. Read More

    Annu Rev Biochem 2018 Apr 18. Epub 2018 Apr 18.
    Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA; email: ,
    Copper-binding metallophores, or chalkophores, play a role in microbial copper homeostasis that is analogous to that of siderophores in iron homeostasis. The best-studied chalkophores are members of the methanobactin (Mbn) family-ribosomally produced, posttranslationally modified natural products first identified as copper chelators responsible for copper uptake in methane-oxidizing bacteria. To date, Mbns have been characterized exclusively in those species, but there is genomic evidence for their production in a much wider range of bacteria. Read More

    Regulation of Clathrin-Mediated Endocytosis.
    Annu Rev Biochem 2018 Apr 16. Epub 2018 Apr 16.
    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; email: , , , ,
    Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian cells. It is responsible for the uptake of transmembrane receptors and transporters, for remodeling plasma membrane composition in response to environmental changes, and for regulating cell surface signaling. CME occurs via the assembly and maturation of clathrin-coated pits that concentrate cargo as they invaginate and pinch off to form clathrin-coated vesicles. Read More

    Structure and Function of the 26S Proteasome.
    Annu Rev Biochem 2018 Apr 13. Epub 2018 Apr 13.
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA; email:
    As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Read More

    Regulated Proteolysis in Bacteria.
    Annu Rev Biochem 2018 Apr 12. Epub 2018 Apr 12.
    Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA; email: ,
    Regulated proteolysis is a vital process that affects all living things. Bacteria use energy-dependent AAA+ proteases to power degradation of misfolded and native regulatory proteins. Given that proteolysis is an irreversible event, specificity and selectivity in degrading substrates are key. Read More

    The Oxysterol-Binding Protein Cycle: Burning Off PI(4)P to Transport Cholesterol.
    Annu Rev Biochem 2018 Mar 29. Epub 2018 Mar 29.
    Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR 7275, Université Côte d'Azur, 06560 Valbonne, France; email:
    To maintain an asymmetric distribution of ions across membranes, protein pumps displace ions against their concentration gradient by using chemical energy. Here, we describe a functionally analogous but topologically opposite process that applies to the lipid transfer protein (LTP) oxysterolbinding protein (OSBP). This multidomain protein exchanges cholesterol for the phosphoinositide phosphatidylinositol 4-phosphate [PI(4)P] between two apposed membranes. Read More

    Imaging Bacterial Cell Wall Biosynthesis.
    Annu Rev Biochem 2018 Mar 29. Epub 2018 Mar 29.
    Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
    Peptidoglycan is an essential component of the cell wall that protects bacteria from environmental stress. A carefully coordinated biosynthesis of peptidoglycan during cell elongation and division is required for cell viability. This biosynthesis involves sophisticated enzyme machineries that dynamically synthesize, remodel, and degrade peptidoglycan. Read More

    Understanding and Improving the Activity of Flavin-Dependent Halogenases via Random and Targeted Mutagenesis.
    Annu Rev Biochem 2018 Mar 28. Epub 2018 Mar 28.
    Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA; email:
    Flavin-dependent halogenases (FDHs) catalyze the halogenation of organic substrates by coordinating reactions of reduced flavin, molecular oxygen, and chloride. Targeted and random mutagenesis of these enzymes have been used to both understand and alter their reactivity. These studies have led to insights into residues essential for catalysis and FDH variants with improved stability, expanded substrate scope, and altered site selectivity. Read More

    Regulation of RNA Polymerase I Transcription in Development, Disease, and Aging.
    Annu Rev Biochem 2018 Mar 28. Epub 2018 Mar 28.
    Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University, 07745 Jena, Germany; email: ,
    Ribosome biogenesis is a complex and highly energy-demanding process that requires the concerted action of all three nuclear RNA polymerases (Pol I-III) in eukaryotes. The three largest ribosomal RNAs (rRNAs) originate from a precursor transcript (pre-rRNA) that is encoded by multicopy genes located in the nucleolus. Transcription of these rRNA genes (rDNA) by Pol I is the key regulation step in ribosome production and is tightly controlled by an intricate network of signaling pathways and epigenetic mechanisms. Read More

    Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design.
    Annu Rev Biochem 2018 Mar 23. Epub 2018 Mar 23.
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA; email:
    Genetic information is translated into proteins by the ribosome. Structural studies of the ribosome and of its complexes with factors and inhibitors have provided invaluable information on the mechanism of protein synthesis. Ribosome inhibitors are among the most successful antimicrobial drugs and constitute more than half of all medicines used to treat infections. Read More

    Directed Evolution of Protein Catalysts.
    Annu Rev Biochem 2018 Mar 1. Epub 2018 Mar 1.
    Laboratory of Organic Chemistry, ETH Zürich, CH-8093 Zürich, Switzerland; email: ,
    Directed evolution is a powerful technique for generating tailor-made enzymes for a wide range of biocatalytic applications. Following the principles of natural evolution, iterative cycles of mutagenesis and screening or selection are applied to modify protein properties, enhance catalytic activities, or develop completely new protein catalysts for non-natural chemical transformations. This review briefly surveys the experimental methods used to generate genetic diversity and screen or select for improved enzyme variants. Read More

    Defining Adult Stem Cells by Function, Not by Phenotype.
    Annu Rev Biochem 2018 Mar 1. Epub 2018 Mar 1.
    Centre for Stem Cells and Regenerative Medicine, King's College London, London SE1 9RT, United Kingdom; email:
    Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells. Read More

    2-Oxoglutarate-Dependent Oxygenases.
    Annu Rev Biochem 2018 Mar 1. Epub 2018 Mar 1.
    The Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3TA, United Kingdom; email:
    2-Oxoglutarate (2OG)-dependent oxygenases (2OGXs) catalyze a remarkably diverse range of oxidative reactions. In animals, these comprise hydroxylations and N-demethylations proceeding via hydroxylation; in plants and microbes, they catalyze a wider range including ring formations, rearrangements, desaturations, and halogenations. The catalytic flexibility of 2OGXs is reflected in their biological functions. Read More

    Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism.
    Annu Rev Biochem 2018 Mar 1. Epub 2018 Mar 1.
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland 20892, USA; email:
    The number of DNA polymerases identified in each organism has mushroomed in last two decades. Most newly found DNA polymerases specialize in translesion synthesis and DNA repair instead of replication. Although intrinsic error rates are higher for translesion and repair polymerases than for replicative polymerases, the specialized polymerases increase genome stability and reduce tumorigenesis. Read More

    Lipid Cell Biology: A Focus on Lipids in Cell Division.
    Annu Rev Biochem 2018 Mar 1. Epub 2018 Mar 1.
    Randall Division of Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King's College London, London SE1 1UL, United Kingdom; email:
    Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Read More

    Principles of Protein Stability and Their Application in Computational Design.
    Annu Rev Biochem 2018 Jan 26. Epub 2018 Jan 26.
    Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel; email:
    Proteins are increasingly used in basic and applied biomedical research.Many proteins, however, are only marginally stable and can be expressed in limited amounts, thus hampering research and applications. Research has revealed the thermodynamic, cellular, and evolutionary principles and mechanisms that underlie marginal stability. Read More

    Protein Quality Control of the Endoplasmic Reticulum and Ubiquitin-Proteasome-Triggered Degradation of Aberrant Proteins: Yeast Pioneers the Path.
    Annu Rev Biochem 2018 Feb 2. Epub 2018 Feb 2.
    Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, 70569 Stuttgart, Germany; email: , ,
    Cells must constantly monitor the integrity of their macromolecular constituents. Proteins are the most versatile class of macromolecules but are sensitive to structural alterations. Misfolded or otherwise aberrant protein structures lead to dysfunction and finally aggregation. Read More

    DNA-Encoded Chemical Libraries: A Selection System Based On Endowing Organic Compounds with Amplifiable Information.
    Annu Rev Biochem 2018 Jan 12. Epub 2018 Jan 12.
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA; email:
    The discovery of organic ligands that bind specifically to proteins is a central problem in chemistry, biology, and the biomedical sciences. The encoding of individual organic molecules with distinctive DNA tags, serving as amplifiable identification bar codes, allows the construction and screening of combinatorial libraries of unprecedented size, thus facilitating the discovery of ligands to many different protein targets. Fundamentally, one links powers of genetics and chemical synthesis. Read More

    Signaling to and from the RNA Polymerase III Transcription and Processing Machinery.
    Annu Rev Biochem 2018 Jan 12. Epub 2018 Jan 12.
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA; email: ,
    RNA polymerase (Pol) III has a specialized role in transcribing the most abundant RNAs in eukaryotic cells, transfer RNAs (tRNAs), along with other ubiquitous small noncoding RNAs, many of which have functions related to the ribosome and protein synthesis. The high energetic cost of producing these RNAs and their central role in protein synthesis underlie the robust regulation of Pol III transcription in response to nutrients and stress by growth regulatory pathways. Downstream of Pol III, signaling impacts posttranscriptional processes affecting tRNA function in translation and tRNA cleavage into smaller fragments that are increasingly attributed with novel cellular activities. Read More

    Lesion Bypass and the Reactivation of Stalled Replication Forks.
    Annu Rev Biochem 2018 Jan 3. Epub 2018 Jan 3.
    Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; email:
    Accurate transmission of the genetic information requires complete duplication of the chromosomal DNA each cell division cycle. However, the idea that replication forks would form at origins of DNA replication and proceed without impairment to copy the chromosomes has proven naive. It is now clear that replication forks stall frequently as a result of encounters between the replication machinery and template damage, slow-moving or paused transcription complexes, unrelieved positive superhelical tension, covalent protein-DNA complexes, and as a result of cellular stress responses. Read More

    Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based Images.
    Annu Rev Biochem 2017 Dec 22. Epub 2017 Dec 22.
    Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut 06520, USA; email: ,
    Super-resolution optical imaging based on the switching and localization of individual fluorescent molecules [photoactivated localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), etc.] has evolved remarkably over the last decade. Originally driven by pushing technological limits, it has become a tool of biological discovery. Read More

    A Solid-State Conceptualization of Information Transfer from Gene to Message to Protein.
    Annu Rev Biochem 2017 Dec 1. Epub 2017 Dec 1.
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9152, USA; email:
    In this review, we describe speculative ideas and early stage research concerning the flow of genetic information from the nuclear residence of genes to the disparate, cytoplasmic sites of protein synthesis. We propose that this process of information transfer is meticulously guided by transient structures formed from protein segments of low sequence complexity/intrinsic disorder. These low complexity domains are ubiquitously associated with regulatory proteins that control gene expression and RNA biogenesis, but they are also found in the central channel of nuclear pores, the nexus points of intermediate filament assembly, and the locations of action of other well-studied cellular proteins and pathways. Read More

    Retrospective on Cholesterol Homeostasis: The Central Role of Scap.
    Annu Rev Biochem 2017 Aug 25. Epub 2017 Aug 25.
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390; email: ,
    Scap is a polytopic membrane protein that functions as a molecular machine to control the cholesterol content of membranes in mammalian cells. In the 21 years since our laboratory discovered Scap, we have learned how it binds sterol regulatory element-binding proteins (SREBPs) and transports them from the endoplasmic reticulum (ER) to the Golgi for proteolytic processing. Proteolysis releases the SREBP transcription factor domains, which enter the nucleus to promote cholesterol synthesis and uptake. Read More

    Biochemistry of Catabolic Reductive Dehalogenation.
    Annu Rev Biochem 2017 Jun;86:357-386
    Department of Civil and Environmental Engineering and Department of Chemical Engineering, Stanford University, Stanford, California 94305; email: ,
    A wide range of phylogenetically diverse microorganisms couple the reductive dehalogenation of organohalides to energy conservation. Key enzymes of such anaerobic catabolic pathways are corrinoid and Fe-S cluster-containing, membrane-associated reductive dehalogenases. These enzymes catalyze the reductive elimination of a halide and constitute the terminal reductases of a short electron transfer chain. Read More

    A New Facet of Vitamin B: Gene Regulation by Cobalamin-Based Photoreceptors.
    Annu Rev Biochem 2017 Jun;86:485-514
    Departamento de Genética y Microbiología, Área de Genética, Unidad Asociada al Instituto de Química Física Rocasolano, Consejo Superior de Investigaciones Científicas, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain; email:
    Living organisms sense and respond to light, a crucial environmental factor, using photoreceptors, which rely on bound chromophores such as retinal, flavins, or linear tetrapyrroles for light sensing. The discovery of photoreceptors that sense light using 5'-deoxyadenosylcobalamin, a form of vitamin B that is best known as an enzyme cofactor, has expanded the number of known photoreceptor families and unveiled a new biological role of this vitamin. The prototype of these B-dependent photoreceptors, the transcriptional repressor CarH, is widespread in bacteria and mediates light-dependent gene regulation in a photoprotective cellular response. Read More

    A Bright Future for Antibiotics?
    Annu Rev Biochem 2017 Jun;86:567-583
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel; email: , ,
    Multidrug resistance is a global threat as the clinically available potent antibiotic drugs are becoming exceedingly scarce. For example, increasing drug resistance among gram-positive bacteria is responsible for approximately one-third of nosocomial infections. As ribosomes are a major target for these drugs, they may serve as suitable objects for novel development of next-generation antibiotics. Read More

    Conceptual and Experimental Tools to Understand Spatial Effects and Transport Phenomena in Nonlinear Biochemical Networks Illustrated with Patchy Switching.
    Annu Rev Biochem 2017 Jun;86:333-356
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125; email:
    Many biochemical systems are spatially heterogeneous and exhibit nonlinear behaviors, such as state switching in response to small changes in the local concentration of diffusible molecules. Systems as varied as blood clotting, intracellular calcium signaling, and tissue inflammation are all heavily influenced by the balance of rates of reaction and mass transport phenomena including flow and diffusion. Transport of signaling molecules is also affected by geometry and chemoselective confinement via matrix binding. Read More

    Metabolite Measurement: Pitfalls to Avoid and Practices to Follow.
    Annu Rev Biochem 2017 Jun;86:277-304
    Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Princeton, New Jersey 08544; email:
    Metabolites are the small biological molecules involved in energy conversion and biosynthesis. Studying metabolism is inherently challenging due to metabolites' reactivity, structural diversity, and broad concentration range. Herein, we review the common pitfalls encountered in metabolomics and provide concrete guidelines for obtaining accurate metabolite measurements, focusing on water-soluble primary metabolites. Read More

    Site-Specific Self-Catalyzed DNA Depurination: A Biological Mechanism That Leads to Mutations and Creates Sequence Diversity.
    Annu Rev Biochem 2017 Jun;86:461-484
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; email: ,
    Self-catalyzed DNA depurination is a sequence-specific physiological mechanism mediated by spontaneous extrusion of a stem-loop catalytic intermediate. Hydrolysis of the 5'G residue of the 5'GA/TGG loop and of the first 5'A residue of the 5'GAGA loop, together with particular first stem base pairs, specifies their hydrolysis without involving protein, cofactor, or cation. As such, this mechanism is the only known DNA catalytic activity exploited by nature. Read More

    Redox-Based Regulation of Bacterial Development and Behavior.
    Annu Rev Biochem 2017 Jun;86:777-797
    Department of Biological Sciences, Columbia University, New York, NY 10027; email:
    Severe changes in the environmental redox potential, and resulting alterations in the oxidation states of intracellular metabolites and enzymes, have historically been considered negative stressors, requiring responses that are strictly defensive. However, recent work in diverse organisms has revealed that more subtle changes in the intracellular redox state can act as signals, eliciting responses with benefits beyond defense and detoxification. Changes in redox state have been shown to influence or trigger chromosome segregation, sporulation, aerotaxis, and social behaviors, including luminescence as well as biofilm establishment and dispersal. Read More

    Mechanisms of Deubiquitinase Specificity and Regulation.
    Annu Rev Biochem 2017 Jun 12;86:159-192. Epub 2017 May 12.
    Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; email:
    Protein ubiquitination is one of the most powerful posttranslational modifications of proteins, as it regulates a plethora of cellular processes in distinct manners. Simple monoubiquitination events coexist with more complex forms of polyubiquitination, the latter featuring many different chain architectures. Ubiquitin can be subjected to further posttranslational modifications (e. Read More

    Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade.
    Annu Rev Biochem 2017 Jun 12;86:27-68. Epub 2017 May 12.
    Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, United Kingdom; email:
    Peptides and proteins have been found to possess an inherent tendency to convert from their native functional states into intractable amyloid aggregates. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidoses. In this review, we describe this field of science with particular reference to the advances that have been made over the last decade in our understanding of its fundamental nature and consequences. Read More

    Mechanisms and Functions of Spatial Protein Quality Control.
    Annu Rev Biochem 2017 Jun 10;86:97-122. Epub 2017 May 10.
    Department of Biology, Stanford University, Stanford, California 94305; email: , ,
    A healthy proteome is essential for cell survival. Protein misfolding is linked to a rapidly expanding list of human diseases, ranging from neurodegenerative diseases to aging and cancer. Many of these diseases are characterized by the accumulation of misfolded proteins in intra- and extracellular inclusions, such as amyloid plaques. Read More

    The Evolution of Organellar Coat Complexes and Organization of the Eukaryotic Cell.
    Annu Rev Biochem 2017 Jun 3;86:637-657. Epub 2017 May 3.
    Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom; email:
    Eukaryotic cells possess a remarkably diverse range of organelles that provide compartmentalization for distinct cellular functions and are likely responsible for the remarkable success of these organisms. The origins and subsequent elaboration of these compartments represent a key aspect in the transition between prokaryotic and eukaryotic cellular forms. The protein machinery required to build, maintain, and define many membrane-bound compartments is encoded by several paralog families, including small GTPases, coiled-bundle proteins, and proteins with β-propeller and α-solenoid secondary structures. Read More

    Proteasomal and Autophagic Degradation Systems.
    Annu Rev Biochem 2017 Jun 1;86:193-224. Epub 2017 May 1.
    Institute of Biochemistry II, School of Medicine, Goethe University, 60598 Frankfurt am Main, Germany; email:
    Autophagy and the ubiquitin-proteasome system are the two major quality control pathways responsible for cellular homeostasis. As such, they provide protection against age-associated changes and a plethora of human diseases. Ubiquitination is utilized as a degradation signal by both systems, albeit in different ways, to mark cargoes for proteasomal and lysosomal degradation. Read More

    Protein Misfolding Diseases.
    Annu Rev Biochem 2017 Jun 24;86:21-26. Epub 2017 Apr 24.
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; email:
    The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies. Read More

    Oxidative Stress.
    Annu Rev Biochem 2017 Jun 24;86:715-748. Epub 2017 Apr 24.
    Department of Medicine, Emory University, Atlanta, Georgia 30322; email:
    Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these converse properties. Redox balance is maintained by prevention, interception, and repair, and concomitantly the regulatory potential of molecular thiol-driven master switches such as Nrf2/Keap1 or NF-κB/IκB is used for system-wide oxidative stress response. Read More

    Cellular Electron Cryotomography: Toward Structural Biology In Situ.
    Annu Rev Biochem 2017 Jun 19;86:873-896. Epub 2017 Apr 19.
    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125; email: ,
    Electron cryotomography (ECT) provides three-dimensional views of macromolecular complexes inside cells in a native frozen-hydrated state. Over the last two decades, ECT has revealed the ultrastructure of cells in unprecedented detail. It has also allowed us to visualize the structures of macromolecular machines in their native context inside intact cells. Read More

    Extracellular Heme Uptake and the Challenge of Bacterial Cell Membranes.
    Annu Rev Biochem 2017 Jun 19;86:799-823. Epub 2017 Apr 19.
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201; email:
    Iron is essential for the survival of most bacteria but presents a significant challenge given its limited bioavailability. Furthermore, the toxicity of iron combined with the need to maintain physiological iron levels within a narrow concentration range requires sophisticated systems to sense, regulate, and transport iron. Most bacteria have evolved mechanisms to chelate and transport ferric iron (Fe) via siderophore receptor systems, and pathogenic bacteria have further lowered this barrier by employing mechanisms to utilize the host's hemoproteins. Read More

    Teaching Old Dyes New Tricks: Biological Probes Built from Fluoresceins and Rhodamines.
    Annu Rev Biochem 2017 Jun 7;86:825-843. Epub 2017 Apr 7.
    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147; email:
    Small-molecule fluorophores, such as fluorescein and rhodamine derivatives, are critical tools in modern biochemical and biological research. The field of chemical dyes is old; colored molecules were first discovered in the 1800s, and the fluorescein and rhodamine scaffolds have been known for over a century. Nevertheless, there has been a renaissance in using these dyes to create tools for biochemistry and biology. Read More

    Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA.
    Annu Rev Biochem 2017 Jun 7;86:541-566. Epub 2017 Apr 7.
    Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan; email: ,
    The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclic GMP-AMP (2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Read More

    Electric Fields and Enzyme Catalysis.
    Annu Rev Biochem 2017 Jun 24;86:387-415. Epub 2017 Mar 24.
    Department of Chemistry, Stanford University, Stanford, California 94305; email:
    What happens inside an enzyme's active site to allow slow and difficult chemical reactions to occur so rapidly? This question has occupied biochemists' attention for a long time. Computer models of increasing sophistication have predicted an important role for electrostatic interactions in enzymatic reactions, yet this hypothesis has proved vexingly difficult to test experimentally. Recent experiments utilizing the vibrational Stark effect make it possible to measure the electric field a substrate molecule experiences when bound inside its enzyme's active site. Read More

    Ubiquitin Ligases: Structure, Function, and Regulation.
    Annu Rev Biochem 2017 Jun 27;86:129-157. Epub 2017 Mar 27.
    Howard Hughes Medical Institute and Department of Pharmacology, University of Washington, Seattle, Washington 98195; email: ,
    Ubiquitin E3 ligases control every aspect of eukaryotic biology by promoting protein ubiquitination and degradation. At the end of a three-enzyme cascade, ubiquitin ligases mediate the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to specific substrate proteins. Early investigations of E3s of the RING (really interesting new gene) and HECT (homologous to the E6AP carboxyl terminus) types shed light on their enzymatic activities, general architectures, and substrate degron-binding modes. Read More

    Engineering and In Vivo Applications of Riboswitches.
    Annu Rev Biochem 2017 Jun 30;86:515-539. Epub 2017 Mar 30.
    Department of Chemistry, University of California, Berkeley, California 94720; email:
    Riboswitches are common gene regulatory units mostly found in bacteria that are capable of altering gene expression in response to a small molecule. These structured RNA elements consist of two modular subunits: an aptamer domain that binds with high specificity and affinity to a target ligand and an expression platform that transduces ligand binding to a gene expression output. Significant progress has been made in engineering novel aptamer domains for new small molecule inducers of gene expression. Read More

    How α-Helical Motifs Form Functionally Diverse Lipid-Binding Compartments.
    Annu Rev Biochem 2017 Jun 30;86:609-636. Epub 2017 Mar 30.
    The Hormel Institute, University of Minnesota, Austin, Minnesota 55912; email: ,
    Lipids are produced site-specifically in cells and then distributed nonrandomly among membranes via vesicular and nonvesicular trafficking mechanisms. The latter involves soluble amphitropic proteins extracting specific lipids from source membranes to function as molecular solubilizers that envelope their insoluble cargo before transporting it to destination sites. Lipid-binding and lipid transfer structural motifs range from multi-β-strand barrels, to β-sheet cups and baskets covered by α-helical lids, to multi-α-helical bundles and layers. Read More

    Isocitrate Dehydrogenase Mutation and (R)-2-Hydroxyglutarate: From Basic Discovery to Therapeutics Development.
    Annu Rev Biochem 2017 Jun 3;86:305-331. Epub 2017 Apr 3.
    Agios Pharmaceuticals Inc., Cambridge, Massachusetts 02139; email: ,
    The identification of heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) in subsets of cancers, including secondary glioblastoma, acute myeloid leukemia, intrahepatic cholangiocarcinoma, and chondrosarcomas, led to intense discovery efforts to delineate the mutations' involvement in carcinogenesis and to develop therapeutics, which we review here. The three IDH isoforms (nicotinamide adenine dinucleotide phosphate-dependent IDH1 and IDH2, and nicotinamide adenine dinucleotide-dependent IDH3) contribute to regulating the circuitry of central metabolism. Several biochemical and genetic observations led to the discovery of the neomorphic production of the oncometabolite (R)-2-hydroxyglutarate (2-HG) by mutant IDH1 and IDH2 (mIDH). Read More

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