2,080 results match your criteria Annual Review Of Biochemistry[Journal]


Detection and Degradation of Stalled Nascent Chains via Ribosome-Associated Quality Control.

Annu Rev Biochem 2020 Jun;89:417-442

Department of Biochemistry, Stanford University, Stanford, California 94305, USA; email:

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 ubiquitylated nascent chains to the proteasome. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-110729DOI Listing

Zona Pellucida Proteins, Fibrils, and Matrix.

Annu Rev Biochem 2020 Jun;89:695-715

Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; email:

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 three-dimensional structure and a ZP domain that consists of two subdomains, ZP-N and ZP-C, with ZP-N of ZP2 and ZP3 required for fibril assembly. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-105310DOI Listing

Biosynthesis and Export of Bacterial Glycolipids.

Annu Rev Biochem 2020 Jun;89:741-768

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22908, USA; email:

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 anchors and facilitators of these transport processes. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-104707DOI Listing

Single-Molecule Studies of Protein Folding with Optical Tweezers.

Annu Rev Biochem 2020 Jun;89:443-470

Department of Biology and Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA; email:

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 which single-molecule kinetic and thermodynamic information about these processes can be extracted. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111442DOI Listing

Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets.

Annu Rev Biochem 2020 Jun;89:45-75

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

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316142PMC

Long Noncoding RNAs: Molecular Modalities to Organismal Functions.

Annu Rev Biochem 2020 Jun;89:283-308

Center for Personal Dynamic Regulomes, Stanford University, Stanford, California 94305, USA.

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012708DOI Listing

Double the Fun, Double the Trouble: Paralogs and Homologs Functioning in the Endoplasmic Reticulum.

Annu Rev Biochem 2020 Jun;89:637-666

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel; email:

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 these differences and characterizing gene-specific functions is complex. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-104831DOI Listing

Structural and Mechanistic Principles of ABC Transporters.

Annu Rev Biochem 2020 Jun;89:605-636

Institute of Biochemistry, Biocenter, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-105201DOI Listing

Standing on the Shoulders of Viruses.

Authors:
Ari Helenius

Annu Rev Biochem 2020 Jun;89:21-43

Institute of Biochemistry, ETH Zurich, Zurich 8093, Switzerland; email:

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 to expand the fundamental understanding of animal viruses and their pathogenic lifestyles. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011320-103928DOI Listing

HLAs, TCRs, and KIRs, a Triumvirate of Human Cell-Mediated Immunity.

Annu Rev Biochem 2020 Jun;89:717-739

Department of Structural Biology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-102754DOI Listing

How Does the Ribosome Fold the Proteome?

Annu Rev Biochem 2020 Jun;89:389-415

Institute of Structural and Molecular Biology, University College London and Birkbeck College, London WC1E 7HX, United Kingdom; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012226DOI Listing

Synthetic Genomes.

Annu Rev Biochem 2020 Jun;89:77-101

Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, NY 10016, USA; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-110704DOI Listing

Christopher Dobson, 1949-2019: Mentor, Friend, Scientist Extraordinaire.

Authors:
Carol V Robinson

Annu Rev Biochem 2020 Jun 28;89:1-19. Epub 2020 Apr 28.

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

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 mechanisms; his collaborative work with physicists to understand the process of protein aggregation; and finally, his later career in which he developed strategies to prevent misfolding. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-105226DOI Listing

Molecular Mechanisms of Facultative Heterochromatin Formation: An X-Chromosome Perspective.

Annu Rev Biochem 2020 Jun 7;89:255-282. Epub 2020 Jul 7.

Directors' Research, EMBL Heidelberg, 69117 Heidelberg, Germany; email:

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 activators. In this review, we discuss the molecular mechanisms underlying the establishment and maintenance of fHC in mammals using a mouse model. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012655DOI Listing

Mucins and the Microbiome.

Authors:
Gunnar C Hansson

Annu Rev Biochem 2020 Jun 3;89:769-793. Epub 2020 Apr 3.

Department of Medical Biochemistry, University of Gothenburg, SE 405 30 Gothenburg, Sweden; email:

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 -glycosylated mucin domains that are diversely decorated by Golgi glycosyltransferases to become extended rodlike structures. The general functions of mucins on internal epithelial surfaces are to wash away microorganisms and, even more importantly, to build protective barriers. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-105053DOI Listing

Molecular Mechanisms of Natural Rubber Biosynthesis.

Annu Rev Biochem 2020 Jun 30;89:821-851. Epub 2020 Mar 30.

Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579, Japan; email:

Natural rubber (NR), principally comprising -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, . In latex, NR is enclosed in rubber particles, which are specialized organelles comprising a hydrophobic NR core surrounded by a lipid monolayer and membrane-bound proteins. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111107DOI Listing

Quantifying Target Occupancy of Small Molecules Within Living Cells.

Annu Rev Biochem 2020 Jun 24;89:557-581. Epub 2020 Mar 24.

Promega Corporation, Madison, Wisconsin 53711, USA; email:

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 an observed phenotype in cultured cells. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011420-092302DOI Listing

Transcription in Living Cells: Molecular Mechanisms of Bursting.

Annu Rev Biochem 2020 Jun 24;89:189-212. Epub 2020 Mar 24.

Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-105250DOI Listing

Current Understanding of the Mechanism of Water Oxidation in Photosystem II and Its Relation to XFEL Data.

Annu Rev Biochem 2020 Jun 24;89:795-820. Epub 2020 Mar 24.

Max-Planck-Institut für Chemische Energiekonversion, 45470 Mülheim an der Ruhr, Germany; email:

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 MnCaO complex, which passes through ≥5 intermediate states in the water-splitting cycle. Spectroscopic techniques complemented by quantum chemical calculations aided in understanding the electronic structure of the cofactor in all (detectable) states of the enzymatic process. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-104801DOI Listing

Evaluating Enhancer Function and Transcription.

Annu Rev Biochem 2020 Jun 20;89:213-234. Epub 2020 Mar 20.

Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

Cell-type- and condition-specific profiles of gene expression require coordination between protein-coding gene promoters and -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 of enhancer loci has identified the molecular features of active enhancers that accompany the binding of transcription factors and local opening of chromatin. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011420-095916DOI Listing

Anti-CRISPRs: Protein Inhibitors of CRISPR-Cas Systems.

Annu Rev Biochem 2020 Jun 18;89:309-332. Epub 2020 Mar 18.

RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA; email:

Clustered regularly interspaced short palindromic repeats (CRISPR) together with their accompanying (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 exploited, leading to their development as highly effective tools for genome editing. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011420-111224DOI Listing

Checkpoint Responses to DNA Double-Strand Breaks.

Annu Rev Biochem 2020 Jun 16;89:103-133. Epub 2020 Mar 16.

Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14853, USA; email:

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 inheritance of unrepaired and broken chromosomes. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-104722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311309PMC

Imaging of DNA and RNA in Living Eukaryotic Cells to Reveal Spatiotemporal Dynamics of Gene Expression.

Annu Rev Biochem 2020 Jun 16;89:159-187. Epub 2020 Mar 16.

Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-104955DOI Listing

The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.

Annu Rev Biochem 2020 Jun 13;89:667-693. Epub 2020 Mar 13.

Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA; email:

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 family members are likely to be potentially unique targets for treating other diseases as well. Read More

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http://dx.doi.org/10.1146/annurev-biochem-011520-105234DOI Listing

Chemical Biology Framework to Illuminate Proteostasis.

Annu Rev Biochem 2020 Jun 25;89:529-555. Epub 2020 Feb 25.

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

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, and what types of biophysical issues each proteostasis network component is capable of addressing remains immature. We describe a chemical biology-informed framework for studying cellular proteostasis that relies on selection of interesting protein-folding problems and precise researcher control of proteostasis network composition and activities. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311290PMC

Mitochondrial Proteases: Multifaceted Regulators of Mitochondrial Plasticity.

Annu Rev Biochem 2020 Jun 19;89:501-528. Epub 2020 Feb 19.

Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; email:

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 the activity of mitochondrial proteins by protein processing, and mediate the degradation of damaged proteins. Read More

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http://dx.doi.org/10.1146/annurev-biochem-062917-012739DOI Listing

Mechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis.

Annu Rev Biochem 2020 Jun 14;89:471-499. Epub 2020 Jan 14.

Institut für Zytobiologie, Philipps-Universität Marburg, 35032 Marburg, Germany; email:

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 iron-sulfur cluster assembly (ISC) machinery and has been dissected into three major steps: de novo synthesis of a [2Fe-2S] cluster on a scaffold protein; Hsp70 chaperone-mediated trafficking of the cluster and insertion into [2Fe-2S] target apoproteins; and catalytic conversion of the [2Fe-2S] into a [4Fe-4S] cluster and subsequent insertion into recipient apoproteins. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111540DOI Listing

Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming.

Annu Rev Biochem 2020 Jun 13;89:235-253. Epub 2020 Jan 13.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA; email:

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 players in this cell type-specific chromatin organization. Read More

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http://dx.doi.org/10.1146/annurev-biochem-120219-103641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311296PMC

Structure and Mechanism of P-Type ATPase Ion Pumps.

Annu Rev Biochem 2020 Jun 24;89:583-603. Epub 2020 Dec 24.

Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark; email:

P-type ATPases are found in all kingdoms of life and constitute a wide range of cation transporters, primarily for H, Na, K, Ca, 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 of P2-ATPases including Ca-ATPases and Na,K-ATPase. Read More

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http://dx.doi.org/10.1146/annurev-biochem-010611-112801DOI Listing

How Is Precursor Messenger RNA Spliced by the Spliceosome?

Annu Rev Biochem 2020 Jun 9;89:333-358. Epub 2019 Dec 9.

Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China; email:

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 metalloribozyme. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111024DOI Listing

Role of Mammalian DNA Methyltransferases in Development.

Annu Rev Biochem 2020 Jun 9;89:135-158. Epub 2019 Dec 9.

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts 02115, USA; email:

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 de novo and maintenance DNA methylation. Read More

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http://dx.doi.org/10.1146/annurev-biochem-103019-102815DOI Listing
June 2020
30.283 Impact Factor

RNA Splicing by the Spliceosome.

Annu Rev Biochem 2020 Jun 3;89:359-388. Epub 2019 Dec 3.

MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-091719-064225DOI Listing

The Organizing Principles of Eukaryotic Ribosome Recruitment.

Annu Rev Biochem 2019 06;88:307-335

Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada; email: ,

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. 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-013118-111042DOI Listing
June 2019
13 Reads

Exosomes.

Annu Rev Biochem 2019 06;88:487-514

Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, USA; email:

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. Exosome biogenesis is a mechanism of protein quality control, and once released, exosomes have activities as diverse as remodeling the extracellular matrix and transmitting signals and molecules to other cells. 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-013118-111902DOI Listing
June 2019
16 Reads

Eukaryotic Base Excision Repair: New Approaches Shine Light on Mechanism.

Annu Rev Biochem 2019 06;88:137-162

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, North Carolina 27709-2233, USA; email:

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111315DOI Listing
June 2019
1 Read
30.283 Impact Factor

Redox Chemistry in the Genome: Emergence of the [4Fe4S] Cofactor in Repair and Replication.

Annu Rev Biochem 2019 06;88:163-190

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

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] cluster versus the reduced [4Fe4S] cluster. This redox switch can be activated from a distance using DNA charge transport (DNA CT) chemistry. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-110644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590699PMC
June 2019
1 Read

Moving Through Barriers in Science and Life.

Authors:
Judith P Klinman

Annu Rev Biochem 2019 06;88:1-24

Department of Chemistry, Department of Molecular and Cell Biology, and California Institute of Quantitative Biosciences (QB3), University of California, Berkeley, California 94720, USA; email:

This first serious attempt at an autobiographical accounting has forced me to sit still long enough to compile my thoughts about a long personal and scientific journey. I especially hope that my trajectory will be of interest and perhaps beneficial to much younger women who are just getting started in their careers. To paraphrase from Virginia Woolf's writings in at the beginning of the 20th century, "for most of history Anonymous was a Woman. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956981PMC
June 2019
2 Reads

Lysosomal Glycosphingolipid Storage Diseases.

Annu Rev Biochem 2019 06;88:461-485

LIMES Institute, Membrane Biology and Lipid Biochemistry Unit, Universität Bonn, D-53121 Bonn, Germany; email: ,

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. Read More

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http://dx.doi.org/10.1146/annurev-biochem-013118-111518DOI Listing
June 2019
8 Reads

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

Annu Rev Biochem 2019 06 24;88:605-633. 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
June 2019
3 Reads
30.283 Impact Factor

Biophysical Techniques in Structural Biology.

Annu Rev Biochem 2019 06 15;88:25-33. 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. 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
June 2019
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Horizontal Cell Biology: Monitoring Global Changes of Protein Interaction States with the Proteome-Wide Cellular Thermal Shift Assay (CETSA).

Annu Rev Biochem 2019 06 2;88:383-408. 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
June 2019
22 Reads

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

Annu Rev Biochem 2019 06 27;88:221-245. Epub 2019 Mar 27.

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

Mutations in the and 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004434PMC
June 2019
2 Reads

Glycoengineering of Antibodies for Modulating Functions.

Annu Rev Biochem 2019 06 27;88:433-459. 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 -linked oligosaccharides (-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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923169PMC
June 2019
9 Reads

Propagation of Protein Aggregation in Neurodegenerative Diseases.

Annu Rev Biochem 2019 06 27;88:785-810. 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
June 2019
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Cancer Treatment in the Genomic Era.

Annu Rev Biochem 2019 06 22;88:247-280. Epub 2019 Mar 22.

Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge CB2 0QQ, United Kingdom; 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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https://www.annualreviews.org/doi/10.1146/annurev-biochem-06
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http://dx.doi.org/10.1146/annurev-biochem-062917-011840DOI Listing
June 2019
6 Reads

Membrane Protein-Lipid Interactions Probed Using Mass Spectrometry.

Annu Rev Biochem 2019 06 22;88:85-111. 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
June 2019
21 Reads

Structure and Mechanisms of F-Type ATP Synthases.

Annu Rev Biochem 2019 06 22;88:515-549. Epub 2019 Mar 22.

Department of Structural Biology, Max Planck Institute of Biophysics, 60438 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
June 2019
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Evaluating and Enhancing Target Specificity of Gene-Editing Nucleases and Deaminases.

Annu Rev Biochem 2019 06 18;88:191-220. 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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https://www.annualreviews.org/doi/10.1146/annurev-biochem-01
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http://dx.doi.org/10.1146/annurev-biochem-013118-111730DOI Listing
June 2019
38 Reads

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

Annu Rev Biochem 2019 06 18;88:725-783. Epub 2019 Mar 18.

Division of Chemistry and Chemical Engineering, California Institute of Technology, 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588426PMC
June 2019
1 Read

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

Annu Rev Biochem 2019 06 3;88:59-83. Epub 2019 Apr 3.

Department of Chemistry and Molecular Biology, University of Gothenburg, 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- retinal chromophore being photoisomerized to a 13- 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
June 2019
26 Reads