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  • A proposed gear mechanism for torque generation in the flagellar motor
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-21
    Keiichi Namba

    In situ structures of the spirochete flagellar motor by cryo-ET reveal two distinct modes of interactions between the rotor ring and stator units. Together with new cryo-EM structures of the isolated stator units, this work provides insights into the mechanisms of torque generation and directional switch.

    更新日期:2020-09-21
  • Quantifying the dynamics of IRES and cap translation with single-molecule resolution in live cells
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-21
    Amanda Koch; Luis Aguilera; Tatsuya Morisaki; Brian Munsky; Timothy J. Stasevich

    Viruses use internal ribosome entry sites (IRES) to hijack host ribosomes and promote cap-independent translation. Although they are well-studied in bulk, the dynamics of IRES-mediated translation remain unexplored at the single-molecule level. Here, we developed a bicistronic biosensor encoding distinct repeat epitopes in two open reading frames (ORFs), one translated from the 5′ cap, and the other

    更新日期:2020-09-21
  • Single-gene imaging links genome topology, promoter–enhancer communication and transcription control
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-21
    Jieru Li; Angela Hsu; Yujing Hua; Guanshi Wang; Lingling Cheng; Hiroshi Ochiai; Takashi Yamamoto; Alexandros Pertsinidis

    Transcription activation by distal enhancers is essential for cell-fate specification and maintenance of cellular identities. How long-range gene regulation is physically achieved, especially within complex regulatory landscapes of non-binary enhancer–promoter configurations, remains elusive. Recent nanoscopy advances have quantitatively linked promoter kinetics and ~100- to 200-nm-sized clusters of

    更新日期:2020-09-21
  • BAK core dimers bind lipids and can be bridged by them
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-14
    Angus D. Cowan; Nicholas A. Smith; Jarrod J. Sandow; Eugene A. Kapp; Yepy H. Rustam; James M. Murphy; Jason M. Brouwer; Jonathan P. Bernardini; Michael J. Roy; Ahmad Z. Wardak; Iris K. Tan; Andrew I. Webb; Jacqueline M. Gulbis; Brian J. Smith; Gavin E. Reid; Grant Dewson; Peter M. Colman; Peter E. Czabotar

    BAK and BAX are essential mediators of apoptosis that oligomerize in response to death cues, thereby causing permeabilization of the mitochondrial outer membrane. Their transition from quiescent monomers to pore-forming oligomers involves a well-characterized symmetric dimer intermediate. However, no essential secondary interface that can be disrupted by mutagenesis has been identified. Here we describe

    更新日期:2020-09-14
  • Structures of mouse DUOX1–DUOXA1 provide mechanistic insights into enzyme activation and regulation
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-14
    Ji Sun

    DUOX1, an NADPH oxidase family member, catalyzes the production of hydrogen peroxide. DUOX1 is expressed in various tissues, including the thyroid and respiratory tract, and plays a crucial role in processes such as thyroid hormone biosynthesis and innate host defense. DUOX1 co-assembles with its maturation factor DUOXA1 to form an active enzyme complex. However, the molecular mechanisms for activation

    更新日期:2020-09-14
  • Cryo-EM structure of the entire mammalian F-type ATP synthase
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-14
    Gergely Pinke; Long Zhou; Leonid A. Sazanov

    The majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo, determined by cryo-electron microscopy. Subunits in the membrane domain are arranged in the ‘proton translocation cluster’ attached to the c-ring and a more distant

    更新日期:2020-09-14
  • Multi-contact 3C reveals that the human genome during interphase is largely not entangled
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-14
    Filipe Tavares-Cadete; Davood Norouzi; Bastiaan Dekker; Yu Liu; Job Dekker

    During interphase, the eukaryotic genome is organized into chromosome territories that are spatially segregated into compartment domains. The extent to which interacting domains or chromosomes are entangled is not known. We analyze series of co-occurring chromatin interactions using multi-contact 3C (MC-3C) in human cells to provide insights into the topological entanglement of chromatin. Multi-contact

    更新日期:2020-09-14
  • Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-14
    Rodrigo Gallardo; Matthew G. Iadanza; Yong Xu; George R. Heath; Richard Foster; Sheena E. Radford; Neil A. Ranson

    Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark of type-2 diabetes (T2D). While no causal link between T2D and amyloid has been established, the S20G mutation in amylin is associated with early-onset T2D. Here we report cryo-EM structures of amyloid fibrils of wild-type human amylin and its S20G variant. The wild-type fibril structure, solved to 3.6-Å resolution

    更新日期:2020-09-14
  • SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-09
    Katharina Schubert; Evangelos D. Karousis; Ahmad Jomaa; Alain Scaiola; Blanca Echeverria; Lukas-Adrian Gurzeler; Marc Leibundgut; Volker Thiel; Oliver Mühlemann; Nenad Ban

    The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the

    更新日期:2020-09-10
  • Atomic-resolution structure of HIV-1 capsid tubes by magic-angle spinning NMR
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-08
    Manman Lu; Ryan W. Russell; Alexander J. Bryer; Caitlin M. Quinn; Guangjin Hou; Huilan Zhang; Charles D. Schwieters; Juan R. Perilla; Angela M. Gronenborn; Tatyana Polenova

    HIV-1 capsid plays multiple key roles in viral replication, and inhibition of capsid assembly is an attractive target for therapeutic intervention. Here, we report the atomic-resolution structure of capsid protein (CA) tubes, determined by magic-angle spinning NMR and data-guided molecular dynamics simulations. Functionally important regions, including the NTD β-hairpin, the cyclophilin A-binding loop

    更新日期:2020-09-09
  • Endogenous retroviruses drive species-specific germline transcriptomes in mammals
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-07
    Akihiko Sakashita; So Maezawa; Kazuki Takahashi; Kris G. Alavattam; Masashi Yukawa; Yueh-Chiang Hu; Shohei Kojima; Nicholas F. Parrish; Artem Barski; Mihaela Pavlicev; Satoshi H. Namekawa

    Gene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species and speciation. Male germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition and have been subject to evolutionary divergence among mammals. However, the mechanisms underlying germline regulatory divergence remain undetermined. Here, we show that endogenous

    更新日期:2020-09-08
  • Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-07
    So Maezawa; Akihiko Sakashita; Masashi Yukawa; Xiaoting Chen; Kazuki Takahashi; Kris G. Alavattam; Ippo Nakata; Matthew T. Weirauch; Artem Barski; Satoshi H. Namekawa

    Owing to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. By analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super-enhancers (SEs) drives bursts in germline gene expression after the mitosis-to-meiosis transition. SE reorganization is regulated by two molecular events:

    更新日期:2020-09-08
  • Mechanisms for target recognition and cleavage by the Cas12i RNA-guided endonuclease
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-07
    Heng Zhang; Zhuang Li; Renjian Xiao; Leifu Chang

    Cas12i is a recently identified type V CRISPR-Cas endonuclease that predominantly cleaves the non-target strand of a double-stranded DNA substrate. This nicking activity of Cas12i could potentially be used for genome editing with high specificity. To elucidate its mechanisms for target recognition and cleavage, we determined cryo-EM structures of Cas12i in multiple functional states. Cas12i pre-orders

    更新日期:2020-09-08
  • Molecular mechanism for rotational switching of the bacterial flagellar motor
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-07
    Yunjie Chang; Kai Zhang; Brittany L. Carroll; Xiaowei Zhao; Nyles W. Charon; Steven J. Norris; Md A. Motaleb; Chunhao Li; Jun Liu

    The bacterial flagellar motor can rotate in counterclockwise (CCW) or clockwise (CW) senses, and transitions are controlled by the phosphorylated form of the response regulator CheY (CheY-P). To dissect the mechanism underlying flagellar rotational switching, we use Borrelia burgdorferi as a model system to determine high-resolution in situ motor structures in cheX and cheY3 mutants, in which motors

    更新日期:2020-09-08
  • Two HIRA-dependent pathways mediate H3.3 de novo deposition and recycling during transcription
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-09-07
    Júlia Torné; Dominique Ray-Gallet; Ekaterina Boyarchuk; Mickaël Garnier; Patricia Le Baccon; Antoine Coulon; Guillermo A. Orsi; Geneviève Almouzni

    Nucleosomes represent a challenge in regard to transcription. Histone eviction enables RNA polymerase II (RNAPII) progression through DNA, but compromises chromatin integrity. Here, we used the SNAP-tag system to distinguish new and old histones and monitor chromatin reassembly coupled to transcription in human cells. We uncovered a transcription-dependent loss of old histone variants H3.1 and H3.3

    更新日期:2020-09-08
  • Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-31
    Simon A Fromm,Rosalie E Lawrence,James H Hurley

    The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin (FLCN) complex (LFC) consists of the inactive Rag dimer, the pentameric scaffold Ragulator, and the FLCN:FNIP2 (FLCN-interacting protein 2) GTPase activating protein (GAP) complex, and prevents Rag dimer activation

    更新日期:2020-08-31
  • Author Correction: SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-26
    Antoni G Wrobel,Donald J Benton,Pengqi Xu,Chloë Roustan,Stephen R Martin,Peter B Rosenthal,John J Skehel,Steven J Gamblin

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-27
  • Structure of DNA polymerase ζ: capturing the getaway driver.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-25
    M Todd Washington,Melissa S Gildenberg

    During translesion synthesis, eukaryotic DNA polymerase ζ carries out extension from a wide range of DNA lesions. Elucidation of the cryo-EM structure of polymerase ζ reveals how the enzyme catalyzes DNA strand synthesis beyond the lesion.

    更新日期:2020-08-25
  • Cryo-EM reveals the transition of Arp2/3 complex from inactive to nucleation-competent state.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-24
    Mohammed Shaaban,Saikat Chowdhury,Brad J Nolen

    Arp2/3 complex, a crucial actin filament nucleator, undergoes structural rearrangements during activation by nucleation-promoting factors (NPFs). However, the conformational pathway leading to the nucleation-competent state is unclear due to lack of high-resolution structures of the activated state. Here we report a ~3.9 Å resolution cryo-EM structure of activated Schizosaccharomyces pombe Arp2/3 complex

    更新日期:2020-08-24
  • Water route for proton pumping in mitochondrial complex I.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-21
    Alexander Galkin

    A new cryo-EM structure of mitochondrial complex I reveals ordered water molecules that connect key elements of the proton-translocating machinery. Analysis of the ubiquinone-binding site of complex I offers insights into the mechanism of catalytic turnover and the regulation of this essential metabolic enzyme.

    更新日期:2020-08-22
  • Ribosomes clear the way for siRNA targeting
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-19
    Ewelina M. Małecka; Sarah A. Woodson

    Visualizing siRNA targeting of single mRNAs in living cells reveals that passing ribosomes temporarily unfold the mRNA, exposing it to siRNA recognition. This effect is due to the slow reorganization of many weak, suboptimal interactions within the mRNA.

    更新日期:2020-08-19
  • Hijacking of endocytosis by HIV-1 Nef is becoming crystal clear
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-19
    Yunan C. Januário; Luis L. P. daSilva

    The cell surface protein CD4 acts as a coreceptor for incoming HIV particles. However, the expression of CD4 in HIV-producing cells is detrimental to virus propagation and pathogenicity. To solve this issue, the viral accessory protein Nef forces CD4 endocytosis and targets it for lysosomal degradation. Structural elucidation of the AP-2–Nef–CD4 complex shows how Nef connects CD4 to the clathrin endocytic

    更新日期:2020-08-19
  • Concentration-dependent splicing is enabled by Rbfox motifs of intermediate affinity.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-17
    Bridget E Begg,Marvin Jens,Peter Y Wang,Christine M Minor,Christopher B Burge

    The Rbfox family of splicing factors regulate alternative splicing during animal development and in disease, impacting thousands of exons in the maturing brain, heart and muscle. Rbfox proteins have long been known to bind to the RNA sequence GCAUG with high affinity and specificity, but just half of Rbfox binding sites contain a GCAUG motif in vivo. We incubated recombinant RBFOX2 with over 60,000

    更新日期:2020-08-17
  • Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-17
    Radhika Malik,Mykhailo Kopylov,Yacob Gomez-Llorente,Rinku Jain,Robert E Johnson,Louise Prakash,Satya Prakash,Iban Ubarretxena-Belandia,Aneel K Aggarwal

    DNA polymerase ζ (Polζ) belongs to the same B-family as high-fidelity replicative polymerases, yet is specialized for the extension reaction in translesion DNA synthesis (TLS). Despite its importance in TLS, the structure of Polζ is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Polζ holoenzyme in the act of DNA synthesis (3.1 Å) and without DNA (4.1 Å). Polζ displays a pentameric

    更新日期:2020-08-17
  • Large-scale tethered function assays identify factors that regulate mRNA stability and translation.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-17
    En-Ching Luo,Jason L Nathanson,Frederick E Tan,Joshua L Schwartz,Jonathan C Schmok,Archana Shankar,Sebastian Markmiller,Brian A Yee,Shashank Sathe,Gabriel A Pratt,Duy B Scaletta,Yuanchi Ha,David E Hill,Stefan Aigner,Gene W Yeo

    The molecular functions of the majority of RNA-binding proteins (RBPs) remain unclear, highlighting a major bottleneck to a full understanding of gene expression regulation. Here, we develop a plasmid resource of 690 human RBPs that we subject to luciferase-based 3ʹ-untranslated-region tethered function assays to pinpoint RBPs that regulate RNA stability or translation. Enhanced UV-cross-linking and

    更新日期:2020-08-17
  • Author Correction: Structural basis for polyglutamate chain initiation and elongation by TTLL family enzymes.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-13
    Kishore K Mahalingan,E Keith Keenan,Madeleine Strickland,Yan Li,Yanjie Liu,Haydn L Ball,Martin E Tanner,Nico Tjandra,Antonina Roll-Mecak

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-14
  • Publisher Correction: Scaling up dissection of functional RNA elements.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-12
    Marc Bühler,Alex Charles Tuck

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-12
  • New players on the piRNA field.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-12
    Maria Ninova,Katalin Fejes Tóth

    The nuclear piRNA pathway safeguards genome integrity in the germline by silencing transposable elements. Three recent studies have identified new players in the mammalian pathway. Two of these, TEX15 and SPOCD1, might provide a link between piRNA-guided complexes that recognize genomic targets and the molecular machinery that induces DNA methylation and transcriptional repression during mouse spermatogenesis

    更新日期:2020-08-12
  • Direct measurement of lipid membrane disruption connects kinetics and toxicity of Aβ42 aggregation.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-10
    Patrick Flagmeier,Suman De,Thomas C T Michaels,Xiaoting Yang,Alexander J Dear,Cecilia Emanuelsson,Michele Vendruscolo,Sara Linse,David Klenerman,Tuomas P J Knowles,Christopher M Dobson

    The formation of amyloid deposits in human tissues is a defining feature of more than 50 medical disorders, including Alzheimer’s disease. Strong genetic and histological evidence links these conditions to the process of protein aggregation, yet it has remained challenging to identify a definitive connection between aggregation and pathogenicity. Using time-resolved fluorescence microscopy of individual

    更新日期:2020-08-10
  • Structural basis for STAT2 suppression by flavivirus NS5.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-10
    Boxiao Wang,Stephanie Thurmond,Kang Zhou,Maria T Sánchez-Aparicio,Jian Fang,Jiuwei Lu,Linfeng Gao,Wendan Ren,Yanxiang Cui,Ethan C Veit,HeaJin Hong,Matthew J Evans,Seán E O'Leary,Adolfo García-Sastre,Z Hong Zhou,Rong Hai,Jikui Song

    Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral–cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV)

    更新日期:2020-08-10
  • Safeguarding mitochondrial genomes in higher eukaryotes.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-06
    Yi Fu,Marco Tigano,Agnel Sfeir

    Mitochondria respond to DNA damage and preserve their own genetic material in a manner distinct from that of the nucleus but that requires organized mito–nuclear communication. Failure to resolve mtDNA breaks leads to mitochondrial dysfunction and affects host cells and tissues. Here, we review the pathways that safeguard mitochondrial genomes and examine the insights gained from studies of cellular

    更新日期:2020-08-06
  • Structure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-04
    Matthew McCallum,Alexandra C Walls,John E Bowen,Davide Corti,David Veesler

    SARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface and fusion of the viral and host membranes. Prefusion SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design. However, its limited

    更新日期:2020-08-04
  • Scaling up dissection of functional RNA elements.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-03
    Marc Bühler,Alex Charles Tuck

    Translation and mRNA decay are tightly connected processes governing protein production, and their regulation involves an elaborate network of protein factors and sequence elements. A massively parallel RNA-based reporter system now reveals regulatory pathways triggered by 5′ UTR elements and allows dissection of the interplay between translation and mRNA decay.

    更新日期:2020-08-03
  • Structural basis for polyglutamate chain initiation and elongation by TTLL family enzymes.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-03
    Kishore K Mahalingan,E Keith Keenan,Madeleine Strickland,Yan Li,Yanjie Liu,Haydn L Ball,Martin E Tanner,Nico Tjandra,Antonina Roll-Mecak

    Glutamylation, introduced by tubulin tyrosine ligase-like (TTLL) enzymes, is the most abundant modification of brain tubulin. Essential effector proteins read the tubulin glutamylation pattern, and its misregulation causes neurodegeneration. TTLL glutamylases post-translationally add glutamates to internal glutamates in tubulin carboxy-terminal tails (branch initiation, through an isopeptide bond)

    更新日期:2020-08-03
  • The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-03
    Matthew J McBride,Nazar Mashtalir,Evan B Winter,Hai T Dao,Martin Filipovski,Andrew R D'Avino,Hyuk-Soo Seo,Neil T Umbreit,Roodolph St Pierre,Alfredo M Valencia,Kristin Qian,Hayley J Zullow,Jacob D Jaffe,Sirano Dhe-Paganon,Tom W Muir,Cigall Kadoch

    Interactions between chromatin-associated proteins and the histone landscape play major roles in dictating genome topology and gene expression. Cancer-specific fusion oncoproteins, which display unique chromatin localization patterns, often lack classical DNA-binding domains, presenting challenges in identifying mechanisms governing their site-specific chromatin targeting and function. Here we identify

    更新日期:2020-08-03
  • Intrinsic curvature of the HIV-1 CA hexamer underlies capsid topology and interaction with cyclophilin A.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-03
    Tao Ni,Samuel Gerard,Gongpu Zhao,Kyle Dent,Jiying Ning,Jing Zhou,Jiong Shi,Jordan Anderson-Daniels,Wen Li,Sooin Jang,Alan N Engelman,Christopher Aiken,Peijun Zhang

    The mature retrovirus capsid consists of a variably curved lattice of capsid protein (CA) hexamers and pentamers. High-resolution structures of the curved assembly, or in complex with host factors, have not been available. By devising cryo-EM methodologies for exceedingly flexible and pleomorphic assemblies, we have determined cryo-EM structures of apo-CA hexamers and in complex with cyclophilin A

    更新日期:2020-08-03
  • Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-08-03
    Daniel N Grba,Judy Hirst

    Mitochondrial complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from ubiquinone reduction by NADH to drive protons across the energy-transducing inner membrane. Recent cryo-EM analyses of mammalian and yeast complex I have revolutionized structural and mechanistic knowledge and defined structures in different functional states. Here, we describe a 2.7-Å-resolution structure

    更新日期:2020-08-03
  • A thermostable, closed SARS-CoV-2 spike protein trimer.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-31
    Xiaoli Xiong,Kun Qu,Katarzyna A Ciazynska,Myra Hosmillo,Andrew P Carter,Soraya Ebrahimi,Zunlong Ke,Sjors H W Scheres,Laura Bergamaschi,Guinevere L Grice,Ying Zhang,,James A Nathan,Stephen Baker,Leo C James,Helen E Baxendale,Ian Goodfellow,Rainer Doffinger,John A G Briggs

    The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. It exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor-binding site and, subsequently, from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S-protein derivatives are

    更新日期:2020-07-31
  • Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-31
    Daming Zhou,Helen M E Duyvesteyn,Cheng-Pin Chen,Chung-Guei Huang,Ting-Hua Chen,Shin-Ru Shih,Yi-Chun Lin,Chien-Yu Cheng,Shu-Hsing Cheng,Yhu-Chering Huang,Tzou-Yien Lin,Che Ma,Jiandong Huo,Loic Carrique,Tomas Malinauskas,Reinis R Ruza,Pranav N M Shah,Tiong Kit Tan,Pramila Rijal,Robert F Donat,Kerry Godwin,Karen R Buttigieg,Julia A Tree,Julika Radecke,Neil G Paterson,Piyada Supasa,Juthathip Mongkolsapaya

    The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution

    更新日期:2020-07-31
  • An embedded lipid in the multidrug transporter LmrP suggests a mechanism for polyspecificity.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-27
    Vincent Debruycker,Andrew Hutchin,Matthieu Masureel,Emel Ficici,Chloé Martens,Pierre Legrand,Richard A Stein,Hassane S Mchaourab,José D Faraldo-Gómez,Han Remaut,Cédric Govaerts

    Multidrug efflux pumps present a challenge to the treatment of bacterial infections, making it vitally important to understand their mechanism of action. Here, we investigate the nature of substrate binding within Lactococcus lactis LmrP, a prototypical multidrug transporter of the major facilitator superfamily. We determined the crystal structure of LmrP in a ligand-bound outward-open state and observed

    更新日期:2020-07-27
  • Decoding mRNA translatability and stability from the 5' UTR.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-27
    Longfei Jia,Yuanhui Mao,Quanquan Ji,Devin Dersh,Jonathan W Yewdell,Shu-Bing Qian

    Precise control of protein synthesis by engineering sequence elements in 5′ untranslated regions (5′ UTRs) remains a fundamental challenge. To accelerate our understanding of the cis-regulatory code embedded in 5′ UTRs, we devised massively parallel reporter assays from a synthetic messenger RNA library composed of over one million 5′ UTR variants. A completely randomized 10-nucleotide sequence preceding

    更新日期:2020-07-27
  • Structural basis of CD4 downregulation by HIV-1 Nef.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-27
    Yonghwa Kwon,Robyn M Kaake,Ignacia Echeverria,Marissa Suarez,Mohammad Karimian Shamsabadi,Charlotte Stoneham,Peter W Ramirez,Jacob Kress,Rajendra Singh,Andrej Sali,Nevan Krogan,John Guatelli,Xiaofei Jia

    The HIV-1 Nef protein suppresses multiple immune surveillance mechanisms to promote viral pathogenesis and is an attractive target for the development of novel therapeutics. A key function of Nef is to remove the CD4 receptor from the cell surface by hijacking clathrin- and adaptor protein complex 2 (AP2)-dependent endocytosis. However, exactly how Nef does this has been elusive. Here, we describe

    更新日期:2020-07-27
  • Controlling the SARS-CoV-2 spike glycoprotein conformation.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-22
    Rory Henderson,Robert J Edwards,Katayoun Mansouri,Katarzyna Janowska,Victoria Stalls,Sophie M C Gobeil,Megan Kopp,Dapeng Li,Rob Parks,Allen L Hsu,Mario J Borgnia,Barton F Haynes,Priyamvada Acharya

    The coronavirus (CoV) spike (S) protein, involved in viral–host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available

    更新日期:2020-07-22
  • Structural insights into telomere protection and homeostasis regulation by yeast CST complex.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-13
    Yunhui Ge,Zhenfang Wu,Hongwen Chen,Qinglu Zhong,Shaohua Shi,Guohui Li,Jian Wu,Ming Lei

    Budding yeast Cdc13–Stn1–Ten1 (CST) complex plays an essential role in telomere protection and maintenance. Despite extensive studies, only structural information of individual domains of CST is available; the architecture of CST still remains unclear. Here, we report crystal structures of Kluyveromyces lactis Cdc13–telomeric-DNA, Cdc13–Stn1 and Stn1–Ten1 complexes and propose an integrated model depicting

    更新日期:2020-07-13
  • Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-13
    Jiangdong Huo,Audrey Le Bas,Reinis R Ruza,Helen M E Duyvesteyn,Halina Mikolajek,Tomas Malinauskas,Tiong Kit Tan,Pramila Rijal,Maud Dumoux,Philip N Ward,Jingshan Ren,Daming Zhou,Peter J Harrison,Miriam Weckener,Daniel K Clare,Vinod K Vogirala,Julika Radecke,Lucile Moynié,Yuguang Zhao,Javier Gilbert-Jaramillo,Michael L Knight,Julia A Tree,Karen R Buttigieg,Naomi Coombes,Michael J Elmore,Miles W Carroll

    The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely

    更新日期:2020-07-13
  • mRNA structural dynamics shape Argonaute-target interactions.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-13
    Suzan Ruijtenberg,Stijn Sonneveld,Tao Ju Cui,Ive Logister,Dion de Steenwinkel,Yao Xiao,Ian J MacRae,Chirlmin Joo,Marvin E Tanenbaum

    Small interfering RNAs (siRNAs) promote RNA degradation in a variety of processes and have important clinical applications. siRNAs direct cleavage of target RNAs by guiding Argonaute2 (AGO2) to its target site. Target site accessibility is critical for AGO2-target interactions, but how target site accessibility is controlled in vivo is poorly understood. Here, we use live-cell single-molecule imaging

    更新日期:2020-07-13
  • A redox switch regulates the structure and function of anti-apoptotic BFL-1.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-13
    Kyle J Korshavn,Thomas E Wales,Gregory H Bird,John R Engen,Loren D Walensky

    Apoptosis is regulated by BCL-2 family proteins. Anti-apoptotic members suppress cell death by deploying a surface groove to capture the critical BH3 α-helix of pro-apoptotic members. Cancer cells hijack this mechanism by overexpressing anti-apoptotic BCL-2 family proteins to enforce cellular immortality. We previously identified and harnessed a unique cysteine (C55) in the groove of anti-apoptotic

    更新日期:2020-07-13
  • Cryo-EM structures of holo condensin reveal a subunit flip-flop mechanism.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-13
    Byung-Gil Lee,Fabian Merkel,Matteo Allegretti,Markus Hassler,Christopher Cawood,Léa Lecomte,Francis J O'Reilly,Ludwig R Sinn,Pilar Gutierrez-Escribano,Marc Kschonsak,Sol Bravo,Takanori Nakane,Juri Rappsilber,Luis Aragon,Martin Beck,Jan Löwe,Christian H Haering

    Complexes containing a pair of structural maintenance of chromosomes (SMC) family proteins are fundamental for the three-dimensional (3D) organization of genomes in all domains of life. The eukaryotic SMC complexes cohesin and condensin are thought to fold interphase and mitotic chromosomes, respectively, into large loop domains, although the underlying molecular mechanisms have remained unknown. We

    更新日期:2020-07-13
  • SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-09
    Antoni G Wrobel,Donald J Benton,Pengqi Xu,Chloë Roustan,Stephen R Martin,Peter B Rosenthal,John J Skehel,Steven J Gamblin

    SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We

    更新日期:2020-07-09
  • Author Correction: A systems view of spliceosomal assembly and branchpoints with iCLIP.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-08
    Michael Briese,Nejc Haberman,Christopher R Sibley,Rupert Faraway,Andrea S Elser,Anob M Chakrabarti,Zhen Wang,Julian König,David Perera,Vihandha O Wickramasinghe,Ashok R Venkitaraman,Nicholas M Luscombe,Luciano Saieva,Livio Pellizzoni,Christopher W J Smith,Tomaž Curk,Jernej Ule

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-07-08
  • Structural insights into Fe-S protein biogenesis by the CIA targeting complex.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-07-06
    Susanne A Kassube,Nicolas H Thomä

    The cytosolic iron–sulfur (Fe–S) assembly (CIA) pathway is required for the insertion of Fe–S clusters into cytosolic and nuclear client proteins, including many DNA replication and repair factors. The molecular mechanisms of client protein recognition and Fe–S cluster transfer remain unknown. Here, we report crystal structures of the CIA targeting complex (CTC), revealing that its CIAO2B subunit is

    更新日期:2020-07-06
  • Quantification of translation uncovers the functions of the alternative transcriptome.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-29
    Lorenzo Calviello,Antje Hirsekorn,Uwe Ohler

    Translation has a fundamental function in defining the fate of the transcribed genome. RNA-sequencing (RNA-seq) data enable the quantification of complex transcript mixtures, often detecting several transcript isoforms of unknown functions for one gene. Here, we describe ORFquant, a method to annotate and quantify translation at the level of single open reading frames (ORFs), using information from

    更新日期:2020-06-29
  • Subnanometer structures of HIV-1 envelope trimers on aldrithiol-2-inactivated virus particles.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-29
    Ze Li,Wenwei Li,Maolin Lu,Julian Bess,Cara W Chao,Jason Gorman,Daniel S Terry,Baoshan Zhang,Tongqing Zhou,Scott C Blanchard,Peter D Kwong,Jeffrey D Lifson,Walther Mothes,Jun Liu

    The HIV-1 envelope glycoprotein (Env) trimer, composed of gp120 and gp41 subunits, mediates viral entry into cells. Recombinant Env trimers have been studied structurally, but characterization of Env embedded in intact virus membranes has been limited to low resolution. Here, we deploy cryo-electron tomography and subtomogram averaging to determine the structures of Env trimers on aldrithiol-2 (AT-2)-inactivated

    更新日期:2020-06-29
  • Dppa2 and Dppa4 safeguard bivalent chromatin in order to establish a pluripotent epigenome.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-22
    Patrick S L Lim,Eran Meshorer

    Bivalent chromatin domains contain opposing histone modifications that assist cell lineage specification. Two studies report a role for Dppa2 and Dppa4 in the establishment of bivalency and the prevention of de novo DNA methylation at development-related genes in mouse embryonic stem cells.

    更新日期:2020-06-23
  • Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-22
    Mélanie A Eckersley-Maslin,Aled Parry,Marloes Blotenburg,Christel Krueger,Yoko Ito,Valar Nila Roamio Franklin,Masashi Narita,Clive S D'Santos,Wolf Reik

    How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subset of developmentally important bivalent promoters characterized by low expression and poised RNA-polymerase. Differentiation assays reveal that Dppa2/4 double

    更新日期:2020-06-23
  • The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-22
    Hiroto Shimada,Tsukasa Kusakizako,T H Dung Nguyen,Tomohiro Nishizawa,Tomoya Hino,Makoto Tominaga,Osamu Nureki

    Transient receptor potential vanilloid subfamily member 3 (TRPV3) is a temperature-sensitive cation channel. Previous cryo-EM analyses of TRPV3 in detergent micelles or amphipol proposed that the lower gate opens by α-to-π helical transitions of the nearby S6 helix. However, it remains unclear how physiological lipids are involved in the TRPV3 activation. Here we determined the apo state structure

    更新日期:2020-06-23
  • Gating of human TRPV3 in a lipid bilayer.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-22
    Zengqin Deng,Grigory Maksaev,Michael Rau,Zili Xie,Hongzhen Hu,James A J Fitzpatrick,Peng Yuan

    The transient receptor potential cation channel subfamily V member 3 (TRPV3) channel plays a critical role in skin physiology, and mutations in TRPV3 result in the development of a congenital skin disorder, Olmsted syndrome. Here we describe multiple cryo-electron microscopy structures of human TRPV3 reconstituted into lipid nanodiscs, representing distinct functional states during the gating cycle

    更新日期:2020-06-23
  • Dppa2 and Dppa4 counteract de novo methylation to establish a permissive epigenome for development.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-22
    Kristjan H Gretarsson,Jamie A Hackett

    Early mammalian development entails genome-wide epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate DNA methylation dynamics, we coupled a single-cell ratiometric DNA methylation reporter with unbiased CRISPR screening in murine embryonic stem cells (ESCs). We identify key genes and regulatory

    更新日期:2020-06-23
  • Cryo-EM structure and inhibitor design of human IAPP (amylin) fibrils.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-15
    Qin Cao,David R Boyer,Michael R Sawaya,Peng Ge,David S Eisenberg

    Human islet amyloid polypeptide (hIAPP) functions as a glucose-regulating hormone but deposits as amyloid fibrils in more than 90% of patients with type II diabetes (T2D). Here we report the cryo-EM structure of recombinant full-length hIAPP fibrils. The fibril is composed of two symmetrically related protofilaments with ordered residues 14–37. Our hIAPP fibril structure (i) supports the previous hypothesis

    更新日期:2020-06-15
  • Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils.
    Nat. Struct. Mol. Biol. (IF 11.98) Pub Date : 2020-06-15
    Christine Röder,Tatsiana Kupreichyk,Lothar Gremer,Luisa U Schäfer,Karunakar R Pothula,Raimond B G Ravelli,Dieter Willbold,Wolfgang Hoyer,Gunnar F Schröder

    Amyloid deposits consisting of fibrillar islet amyloid polypeptide (IAPP) in pancreatic islets are associated with beta-cell loss and have been implicated in type 2 diabetes (T2D). Here, we applied cryo-EM to reconstruct densities of three dominant IAPP fibril polymorphs, formed in vitro from synthetic human IAPP. An atomic model of the main polymorph, built from a density map of 4.2-Å resolution,

    更新日期:2020-06-15
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