2,042 results match your criteria Annual Review of Biochemistry [Journal]


Small-Molecule-Based Fluorescent Sensors for Selective Detection of Reactive Oxygen Species in Biological Systems.

Annu Rev Biochem 2019 Apr 24. Epub 2019 Apr 24.

Morningside Laboratory for Chemical Biology, Department of Chemistry, The University of Hong Kong, Hong Kong, P. R. China; email: , , , ,

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 uncovering the relevant biological mechanisms and deconvoluting the apparently paradoxical roles of distinct ROS in human health and disease lies in the selective and sensitive detection of these transient species in the complex biological milieu. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111754DOI Listing

Biophysical Techniques in Structural Biology.

Annu Rev Biochem 2019 Apr 15. Epub 2019 Apr 15.

Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom; email:

Over the past six decades, steadily increasing progress in the application of the principles and techniques of the physical sciences to the study of biological systems has led to remarkable insights into the molecular basis of life itself. Of particular significance has been the way in which the determination of the structures and dynamical properties of proteins and nucleic acids has so often led directly to a profound understanding of the nature and mechanism of their functional roles. The increasing number and power of experimental and theoretical techniques that can be applied successfully to living systems is now ushering in a new era of structural biology that is leading to fundamentally new information about the maintenance of health, the origins of disease, and the development of effective strategies for therapeutic intervention. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111947DOI Listing
April 2019
1 Read

Horizontal Cell Biology: Monitoring Global Changes of Protein Interaction States with the Proteome-Wide Cellular Thermal Shift Assay (CETSA).

Annu Rev Biochem 2019 Apr 2. Epub 2019 Apr 2.

School of Biological Sciences, Nanyang Technological University, Singapore 138673; email: , , ,

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 and drug toxicity. Highly sensitive multidimensional MS-CETSA implementations can now also access binding of physiological ligands to proteins, such as metabolites, nucleic acids, and other proteins. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-biochem-06
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http://dx.doi.org/10.1146/annurev-biochem-062917-012837DOI Listing
April 2019
7 Reads

The BRCA Tumor Suppressor Network in Chromosome Damage Repair by Homologous Recombination.

Annu Rev Biochem 2019 Mar 27. Epub 2019 Mar 27.

Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

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 BRCA tumor suppressor network executes its biological functions would provide the foundation for developing targeted cancer therapeutics, but progress in this area has been greatly hampered by the challenge of obtaining purified BRCA complexes for mechanistic studies. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111058DOI Listing
March 2019
1 Read

Glycoengineering of Antibodies for Modulating Functions.

Annu Rev Biochem 2019 Mar 27. Epub 2019 Mar 27.

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA; email: , , , ,

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012911DOI Listing
March 2019
1 Read

Propagation of Protein Aggregation in Neurodegenerative Diseases.

Annu Rev Biochem 2019 Mar 27. Epub 2019 Mar 27.

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas, Southwestern Medical Center, Dallas, Texas 75390, USA; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-061516-045049DOI Listing

Cancer Treatment in the Genomic Era.

Annu Rev Biochem 2019 Mar 22. Epub 2019 Mar 22.

Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, United Kingdom, CB2 0QQ; email: ,

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 with potential therapeutic value. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-011840DOI Listing
March 2019
4 Reads

Membrane Protein-Lipid Interactions Probed Using Mass Spectrometry.

Annu Rev Biochem 2019 Mar 22. Epub 2019 Mar 22.

Department of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom; email:

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. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-biochem-01
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http://dx.doi.org/10.1146/annurev-biochem-013118-111508DOI Listing
March 2019
3 Reads

Structure and Mechanisms of F-Type ATP Synthases.

Annu Rev Biochem 2019 Mar 22. Epub 2019 Mar 22.

Department of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany; email:

FF 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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-110903DOI Listing
March 2019
3 Reads

Evaluating and Enhancing Target Specificity of Gene-Editing Nucleases and Deaminases.

Annu Rev Biochem 2019 Mar 18. Epub 2019 Mar 18.

Center for Genome Engineering, Institute for Basic Science, Daejeon 34126, Republic of Korea; email:

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 off-target activity through the recognition of near-cognate DNA sequences to their target sites, resulting in collateral damage to the genome in the form of local mutagenesis or genomic rearrangements. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111730DOI Listing
March 2019
7 Reads

The Structure of the Nuclear Pore Complex (An Update).

Annu Rev Biochem 2019 Mar 18. Epub 2019 Mar 18.

California Institute of Technology, Division of Chemistry and Chemical Engineering, Pasadena, California 91125, USA; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-011901DOI Listing

Bacteriorhodopsin: Structural Insights Revealed Using X-Ray Lasers and Synchrotron Radiation.

Annu Rev Biochem 2019 Mar 4. Epub 2019 Mar 4.

Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, SE-40530 Gothenburg, Sweden; email:

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 studied by a myriad of biochemical, biophysical, and structural techniques. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111327DOI Listing
March 2019
2 Reads

Integrative Structure Modeling: Overview and Assessment.

Annu Rev Biochem 2019 Mar 4. Epub 2019 Mar 4.

Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel; email:

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 to various biological systems, with a focus on large protein complexes. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111429DOI Listing
March 2019
1 Read

Molecular Mechanism of Cytokinesis.

Annu Rev Biochem 2019 Jan 16. Epub 2019 Jan 16.

Department of Chemical Engineering, Columbia University, New York, NY 10027, USA; email:

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. Interactions of myosin-II with actin filaments produce force to assemble and then constrict the contractile ring to form a cleavage furrow. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012530DOI Listing
January 2019
3 Reads

Lysine-Targeted Inhibitors and Chemoproteomic Probes.

Annu Rev Biochem 2019 Jan 11. Epub 2019 Jan 11.

Department of Cellular and Molecular Pharmacology, University of California San Francisco, California 94158, USA; email: ,

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-061516-044805DOI Listing
January 2019
1 Read

Soluble Methane Monooxygenase.

Annu Rev Biochem 2019 Jan 11. Epub 2019 Jan 11.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA; email:

Aerobic life is possible because the molecular structure of oxygen (O) 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 and temporal selectivity at ambient temperatures through the evolution of oxidase and oxygenase enzymes. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111529DOI Listing
January 2019
3 Reads

Mechanism and Regulation of Centriole and Cilium Biogenesis.

Annu Rev Biochem 2019 Jan 2. Epub 2019 Jan 2.

Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA; email:

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, and locomotion. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111153DOI Listing
January 2019
1 Read

X-Ray Free-Electron Lasers for the Structure and Dynamics of Macromolecules.

Authors:
Henry N Chapman

Annu Rev Biochem 2019 Jan 2. Epub 2019 Jan 2.

Center for Free-Electron Laser Science, DESY, 22607 Hamburg, Germany; email:

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 diffraction measurements of single noncrystalline objects. Initial explorations of this idea and of outrunning radiation damage with femtosecond pulses led to the development of serial crystallography and the ability to obtain high-resolution structures of small crystals without the need for cryogenic cooling. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-110744DOI Listing
January 2019
1 Read

The Hippo Pathway: Biology and Pathophysiology.

Annu Rev Biochem 2018 Dec 19. Epub 2018 Dec 19.

Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA; email: , , ,

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, transcriptional coactivators YAP and TAZ. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111829DOI Listing
December 2018
10 Reads

Eukaryotic Ribosome Assembly.

Annu Rev Biochem 2018 12 19. Epub 2018 Dec 19.

Biochemistry Center, University of Heidelberg, 69120 Heidelberg, Germany; email: ,

Ribosomes, which synthesize the proteins of a cell, comprise ribosomalRNA 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, only recently, due to the revolution in cryo-electron microscopy, could pseudoatomic structures of different preribosomal particles be obtained. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-110817DOI Listing
December 2018
2 Reads

Mechanisms of Cotranslational Maturation of Newly Synthesized Proteins.

Annu Rev Biochem 2018 Dec 3. Epub 2018 Dec 3.

Center for Molecular Biology of Heidelberg University (ZMBH) and German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany; email: ,

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 of machineries that transiently engage nascent polypeptides at distinct phases of translation. Read More

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December 2018
12 Reads

Energy-Coupling Factor-Type ATP-Binding Cassette Transporters.

Annu Rev Biochem 2018 Nov 28. Epub 2018 Nov 28.

Groningen Biomolecular Sciences and Biotechnology Institute , University of Groningen, 9747AG Groningen, The Netherlands; email: , ,

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 over in the membrane when carrying the bound substrate from the extracellular side of the bilayer to the cytosol. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111705DOI Listing
November 2018
1 Read

Botulinum and Tetanus Neurotoxins.

Annu Rev Biochem 2018 Nov 2. Epub 2018 Nov 2.

Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden; email:

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. Read More

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November 2018
12 Reads

Single-Molecule Kinetics in Living Cells.

Annu Rev Biochem 2018 Oct 25. Epub 2018 Oct 25.

Department of Cell and Molecular Biology, Uppsala University, 75124 Uppsala, Sweden; email:

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 kinetics under physiologically relevant conditions. In this review, we illuminate the particular advantages of single-molecule techniques when studying kinetics in living cells and discuss solutions to specific challenges associated with these methods. Read More

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October 2018
3 Reads

Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates.

Annu Rev Biochem 2018 06;87:921-964

Signature Research Programs in Cardiovascular and Metabolic Disorders and Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore 169857.

Protein serine/threonine phosphatases (PPPs) are ancient enzymes, with distinct types conserved across eukaryotic evolution. PPPs are segregated into types primarily on the basis of the unique interactions of PPP catalytic subunits with regulatory proteins. The resulting holoenzymes dock substrates distal to the active site to enhance specificity. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-biochem-06
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http://dx.doi.org/10.1146/annurev-biochem-062917-012332DOI Listing
June 2018
6 Reads

Protein Evolution and Design.

Annu Rev Biochem 2018 06;87:101-103

Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden; email:

This article introduces the Protein Evolution and Design theme of the Annual Review of Biochemistry Volume 87. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012013DOI Listing
June 2018
4 Reads

The Structural Enzymology of Iterative Aromatic Polyketide Synthases: A Critical Comparison with Fatty Acid Synthases.

Annu Rev Biochem 2018 06;87:503-531

Departments of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, California 92697, USA; email:

Polyketides are a large family of structurally complex natural products including compounds with important bioactivities. Polyketides are biosynthesized by polyketide synthases (PKSs), multienzyme complexes derived evolutionarily from fatty acid synthases (FASs). The focus of this review is to critically compare the properties of FASs with iterative aromatic PKSs, including type II PKSs and fungal type I nonreducing PKSs whose chemical logic is distinct from that of modular PKSs. Read More

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http://dx.doi.org/10.1146/annurev-biochem-063011-164509DOI Listing
June 2018
10 Reads

How Messenger RNA and Nascent Chain Sequences Regulate Translation Elongation.

Annu Rev Biochem 2018 06;87:421-449

Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305-5126, USA; email: , , , , ,

Translation elongation is a highly coordinated, multistep, multifactor process that ensures accurate and efficient addition of amino acids to a growing nascent-peptide chain encoded in the sequence of translated messenger RNA (mRNA). Although translation elongation is heavily regulated by external factors, there is clear evidence that mRNA and nascent-peptide sequences control elongation dynamics, determining both the sequence and structure of synthesized proteins. Advances in methods have driven experiments that revealed the basic mechanisms of elongation as well as the mechanisms of regulation by mRNA and nascent-peptide sequences. Read More

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http://dx.doi.org/10.1146/annurev-biochem-060815-014818DOI Listing
June 2018
36 Reads

Chromatin and Metabolism.

Annu Rev Biochem 2018 06;87:27-49

Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA; email: ,

Chromatin is a mighty consumer of cellular energy generated by metabolism. Metabolic status is efficiently coordinated with transcription and translation, which also feed back to regulate metabolism. Conversely, suppression of energy utilization by chromatin processes may serve to preserve energy resources for cell survival. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012634DOI Listing
June 2018
4 Reads

Nuclear Genomic Instability and Aging.

Annu Rev Biochem 2018 06;87:295-322

Department of Molecular Medicine and the Center on Aging, The Scripps Research Institute Florida, Jupiter, Florida 33458, USA; email:

The nuclear genome decays as organisms age. Numerous studies demonstrate that the burden of several classes of DNA lesions is greater in older mammals than in young mammals. More challenging is proving this is a cause rather than a consequence of aging. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012239DOI Listing
June 2018
18 Reads

Protein Quality Control Degradation in the Nucleus.

Annu Rev Biochem 2018 06;87:725-749

Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA; email: ,

Nuclear proteins participate in diverse cellular processes, many of which are essential for cell survival and viability. To maintain optimal nuclear physiology, the cell employs the ubiquitin-proteasome system to eliminate damaged and misfolded proteins in the nucleus that could otherwise harm the cell. In this review, we highlight the current knowledge about the major ubiquitin-protein ligases involved in protein quality control degradation (PQCD) in the nucleus and how they orchestrate their functions to eliminate misfolded proteins in different nuclear subcompartments. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012730DOI Listing
June 2018
22 Reads

Transition Metal Sequestration by the Host-Defense Protein Calprotectin.

Annu Rev Biochem 2018 06;87:621-643

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:

In response to microbial infection, the human host deploys metal-sequestering host-defense proteins, which reduce nutrient availability and thereby inhibit microbial growth and virulence. Calprotectin (CP) is an abundant antimicrobial protein released from neutrophils and epithelial cells at sites of infection. CP sequesters divalent first-row transition metal ions to limit the availability of essential metal nutrients in the extracellular space. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066180PMC
June 2018
21 Reads

Metabolite-Enzyme Coevolution: From Single Enzymes to Metabolic Pathways and Networks.

Annu Rev Biochem 2018 06;87:187-216

Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel; email: ,

How individual enzymes evolved is relatively well understood. However, individual enzymes rarely confer a physiological advantage on their own. Judging by its current state, the emergence of metabolism seemingly demanded the simultaneous emergence of many enzymes. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012023DOI Listing
June 2018
4 Reads

The Molecular Basis of G Protein-Coupled Receptor Activation.

Annu Rev Biochem 2018 06;87:897-919

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA; email:

G protein-coupled receptors (GPCRs) mediate the majority of cellular responses to external stimuli. Upon activation by a ligand, the receptor binds to a partner heterotrimeric G protein and promotes exchange of GTP for GDP, leading to dissociation of the G protein into α and βγ subunits that mediate downstream signals. GPCRs can also activate distinct signaling pathways through arrestins. Read More

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http://dx.doi.org/10.1146/annurev-biochem-060614-033910DOI Listing
June 2018
5 Reads

Reductionist Approach in Peptide-Based Nanotechnology.

Authors:
Ehud Gazit

Annu Rev Biochem 2018 06;87:533-553

Department of Molecular Microbiology and Biotechnology, Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv 6997801, Israel; email:

The formation of ordered nanostructures by molecular self-assembly of proteins and peptides represents one of the principal directions in nanotechnology. Indeed, polyamides provide superior features as materials with diverse physical properties. A reductionist approach allowed the identification of extremely short peptide sequences, as short as dipeptides, which could form well-ordered amyloid-like β-sheet-rich assemblies comparable to supramolecular structures made of much larger proteins. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352959PMC
June 2018
20 Reads

A Lifetime of Adventures in Glycobiology.

Authors:
Stuart Kornfeld

Annu Rev Biochem 2018 06;87:1-21

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

My initial research experience involved studying how bacteria synthesize nucleotide sugars, the donors for the formation of cell wall polysaccharides. During this time, I became aware that mammalian cells also have a surface coat of sugars and was intrigued as to whether these sugars might be arranged in specific sequences that function as information molecules in biologic processes. Thus began a long journey that has taken me from glycan structural analysis and determination of plant lectin-binding preferences to the biosynthesis of Asn-linked oligosaccharides and the mannose 6-phosphate (Man-6-P) lysosomal enzyme targeting pathway. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-011911DOI Listing
June 2018
4 Reads

A Rich Man, Poor Man Story of S-Adenosylmethionine and Cobalamin Revisited.

Annu Rev Biochem 2018 06;87:555-584

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email: ,

S-adenosylmethionine (AdoMet) has been referred to as both "a poor man's adenosylcobalamin (AdoCbl)" and "a rich man's AdoCbl," but today, with the ever-increasing number of functions attributed to each cofactor, both appear equally rich and surprising. The recent characterization of an organometallic species in an AdoMet radical enzyme suggests that the line that differentiates them in nature will be constantly challenged. Here, we compare and contrast AdoMet and cobalamin (Cbl) and consider why Cbl-dependent AdoMet radical enzymes require two cofactors that are so similar in their reactivity. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012500DOI Listing
June 2018
3 Reads

Metabolic Regulation of Transcription and Chromatin.

Authors:
Ronald C Conaway

Annu Rev Biochem 2018 06;87:23-25

Stowers Institute for Medical Research, Kansas City, Missouri, 64110 USA; email:

Although cell metabolism has been established as a major regulator of eukaryotic gene expression, the mechanisms underlying this regulation are still being uncovered. Recent years have seen great advances in our understanding of biochemical mechanisms of metabolic regulation of transcription and chromatin. Prime examples include insights into how nutrients and cellular energy status regulate synthesis of ribosomal RNAs by RNA polymerases I and III during ribosome biogenesis and how a variety of enzymes that catalyze modifications of histones in chromatin are regulated by the levels of certain metabolites. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012600DOI Listing
June 2018
3 Reads

Along the Central Dogma-Controlling Gene Expression with Small Molecules.

Annu Rev Biochem 2018 06 4;87:391-420. 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

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http://dx.doi.org/10.1146/annurev-biochem-060614-033923DOI Listing
June 2018
14 Reads

Ancient Biomolecules and Evolutionary Inference.

Annu Rev Biochem 2018 06 25;87:1029-1060. Epub 2018 Apr 25.

Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark; email: ,

Over the past three decades, studies of ancient biomolecules-particularly ancient DNA, proteins, and lipids-have revolutionized our understanding of evolutionary history. Though initially fraught with many challenges, today the field 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-012002DOI Listing
June 2018
13 Reads

The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.

Annu Rev Biochem 2018 06 25;87:263-294. 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-012415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076887PMC
June 2018
4 Reads

Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs.

Annu Rev Biochem 2018 06 18;87:323-350. Epub 2018 Apr 18.

Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg 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

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https://www.annualreviews.org/doi/10.1146/annurev-biochem-06
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http://dx.doi.org/10.1146/annurev-biochem-062917-011816DOI Listing
June 2018
16 Reads

Chalkophores.

Annu Rev Biochem 2018 06 18;87:645-676. 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-012300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013396PMC
June 2018
6 Reads

Regulation of Clathrin-Mediated Endocytosis.

Annu Rev Biochem 2018 06 16;87:871-896. 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-012644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383209PMC
June 2018
6 Reads

Structure and Function of the 26S Proteasome.

Annu Rev Biochem 2018 06 13;87:697-724. 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-011931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422034PMC
June 2018
9 Reads

Regulated Proteolysis in Bacteria.

Annu Rev Biochem 2018 06 12;87:677-696. 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-012848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013389PMC
June 2018
7 Reads

The Oxysterol-Binding Protein Cycle: Burning Off PI(4)P to Transport Cholesterol.

Annu Rev Biochem 2018 06 29;87:809-837. 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) oxysterol-binding protein (OSBP). This multidomain protein exchanges cholesterol for the phosphoinositide phosphatidylinositol 4-phosphate [PI(4)P] between two apposed membranes. Read More

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http://dx.doi.org/10.1146/annurev-biochem-061516-044924DOI Listing
June 2018
11 Reads

Imaging Bacterial Cell Wall Biosynthesis.

Annu Rev Biochem 2018 06 29;87:991-1014. 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

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https://www.annualreviews.org/doi/10.1146/annurev-biochem-06
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http://dx.doi.org/10.1146/annurev-biochem-062917-012921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287495PMC
June 2018
24 Reads

Understanding and Improving the Activity of Flavin-Dependent Halogenases via Random and Targeted Mutagenesis.

Annu Rev Biochem 2018 06 28;87:159-185. 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-012042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013374PMC
June 2018
12 Reads

Regulation of RNA Polymerase I Transcription in Development, Disease, and Aging.

Annu Rev Biochem 2018 06 28;87:51-73. 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

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http://dx.doi.org/10.1146/annurev-biochem-062917-012612DOI Listing
June 2018
32 Reads