Structural biology articles within Nature Communications

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  • Article
    | Open Access

    Rebelo-Guiomar et al. unveil late stage assembly intermediates of the human mitochondrial ribosome by inactivating the methyltransferase MRM2 in cells. Absence of MRM2 impairs organismal homeostasis, while its catalytic activity is dispensable for mitoribosomal biogenesis.

    • Pedro Rebelo-Guiomar
    • , Simone Pellegrino
    •  & Michal Minczuk
  • Article
    | Open Access

    HAESA and HSL2 are receptors for IDA/IDL-family signaling peptides in plants. Here the authors show that HSL1, previously shown to recognize CLE9, preferentially binds IDA/IDL peptides and regulates leaf epidermal patterning independently of CLE peptides.

    • Andra-Octavia Roman
    • , Pedro Jimenez-Sandoval
    •  & Julia Santiago
  • Article
    | Open Access

    The human neuropeptide Y (NPY) acts through G-protein coupled receptors and is involved in food intake, stress response, anxiety, and memory retention. Here, the authors show that, unlike in other neuropeptides, both the N-terminal and the C-terminal regions of NPY interact with the NPY receptor 1.

    • Chaehee Park
    • , Jinuk Kim
    •  & Hee-Jung Choi
  • Article
    | Open Access

    The interplay of the proteasome and deubiquitinase Ubp6 is crucial for the degradation of ubiquitylated substrates. Here, the authors provide structural insights into the allosteric mechanism by which the activities of both Ubp6 and the proteasome are regulated.

    • Ka Ying Sharon Hung
    • , Sven Klumpe
    •  & Daniel Finley
  • Article
    | Open Access

    The intracellular domain (ICD) of Cys-loop receptors mediates many of their functions, but no complete structure of a Cys-loop receptor ICD is available to date. Here, the authors combine NMR and ESR spectroscopy to determine the full-length ICD structures of the human α7 nicotinic acetylcholine receptor (α7nAChR).

    • Vasyl Bondarenko
    • , Marta M. Wells
    •  & Pei Tang
  • Article
    | Open Access

    Molecular glue has been used as a broad term describing a class of protein interaction-promoting compounds. Here, the authors outline two unifying thermodynamic features to formally define molecular glues and guide their prospective discovery.

    • Shiyun Cao
    • , Shoukai Kang
    •  & Ning Zheng
  • Article
    | Open Access

    AMPA glutamate receptors, mediate the majority of excitatory signaling in the brain. Here the authors show how the auxiliary subunit TARP-γ8 shapes gating kinetics, ion conductance and rectification properties of the heteromeric GluA1/2 AMPA receptor.

    • Beatriz Herguedas
    • , Bianka K. Kohegyi
    •  & Ingo H. Greger
  • Article
    | Open Access

    Liu et al. report structures of human sphingosine 1-phosphate (S1P) receptor 1 (S1P1) in complex with Gi and S1P or the multiple sclerosis (MS) drug Siponimod, as well as human lysophosphatidic acid (LPA) receptor 1 (LPA1) in complex with Gi and LPA, revealing distinct conformations of the lysophospholipids interacting with their cognate GPCRs.

    • Shian Liu
    • , Navid Paknejad
    •  & Xin-Yun Huang
  • Article
    | Open Access

    Neutralizing antibodies (bNAbs) against HIV-1 are exclusively directed against the viral envelope protein (Env) and mainly target Env in a closed, prefusion state. Here, Yang et al. structurally characterize two heterologously-neutralizing CD4-binding site (CD4bs) antibodies isolated from sequentially immunized macaques, and show that these antibodies recognize the CD4bs on Env trimers in an „occluded-open‟ conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4.

    • Zhi Yang
    • , Kim-Marie A. Dam
    •  & Pamela J. Bjorkman
  • Article
    | Open Access

    Tousled-like kinase 2 (TLK2) phosphorylates ASF1 histone chaperones to promote nucleosome assembly in S phase. Here, the authors show that TLK2 targets ASF1 by simulating its client protein histone H3, exploiting a primordial protein interaction surface for regulatory control.

    • Bertrand Simon
    • , Hua Jane Lou
    •  & David A. Calderwood
  • Article
    | Open Access

    Type 2 bradykinin receptor (B2R) is essential in vasodilation and cardioprotection. Here the authors present two cryo-EM structures of human B2R-Gq in complex with bradykinin and kallidin to elucidate the mechanisms for ligand binding, receptor activation, and Gq proteins coupling.

    • Jinkang Shen
    • , Dongqi Zhang
    •  & Haitao Zhang
  • Article
    | Open Access

    The archaellum is a molecular machine used by archaea to swim, consisting of an intracellular motor that drives the rotation of an extracellular filament composed of multiple copies of proteins named archaellins. Here, the authors use electron cryo-microscopy to elucidate the structure of an archaellum, and find that the filament is composed of two alternating archaellins.

    • Lavinia Gambelli
    • , Michail N. Isupov
    •  & Bertram Daum
  • Article
    | Open Access

    HIV envelope is a target for vaccine development, but induction of broadly neutralizing antibodies has been difficult. Here, the authors show that electroporation with a synthetic DNA vaccine construct allows in vivo production of HIV envelope native like trimers to induce autologous tier-2 neutralizing antibodies targeting a C3/V5 epitope in mice.

    • Ziyang Xu
    • , Susanne Walker
    •  & Daniel W. Kulp
  • Article
    | Open Access

     The Arp2/3 complex inhibitor Arpin controls cell migration by interrupting a feedback loop involving Rac-WAVE-Arp2/3 complex Here, the authors use structural, biochemical, and cellular studies to reveal Arpin’s mechanism of inhibition.

    • Fred E. Fregoso
    • , Trevor van Eeuwen
    •  & Roberto Dominguez
  • Article
    | Open Access

    The drug AT-527 targets the SARS-CoV-2 replication machinery. Here the authors use Cryo-EM to show how AT-527 inhibits SARS-CoV-2 polymerase by acting as an immediate RNA chain terminator and stably binding in a NiRAN active-site pocket; impeding an essential nucleotide-transfer activity.

    • Ashleigh Shannon
    • , Véronique Fattorini
    •  & Bruno Canard
  • Article
    | Open Access

    The cell wall of the bacterial pathogen Group A Streptococcus is decorated with a polysaccharide termed GAC, which is a target for vaccine development. Here, Rush et al. characterize the linkage between GAC and peptidoglycan, and identify a protein that deacetylates the linkage and thus protects the pathogen against host cationic antimicrobial proteins.

    • Jeffrey S. Rush
    • , Prakash Parajuli
    •  & Natalia Korotkova
  • Article
    | Open Access

    Many parasitic organisms contain molecular structures that are drastically smaller than analogous structures in non-parasitic organisms. Here the authors describe a cryo-EM structure of the ribosome from E. cuniculi that reveals that it compensated rRNA truncations by evolving the ability to use small molecules as ribosomal building blocks.

    • David Nicholson
    • , Marco Salamina
    •  & Sergey V. Melnikov
  • Article
    | Open Access

    The catalytic domains in nonribosomal peptide synthetases (NRPSs) are responsible for a choreography of events that elongates substrates into natural products. Here, the authors present cryo-EM structures of a siderophore-producing dimeric NRPS elongation module in multiple distinct conformations, which provides insight into the mechanisms of catalytic trajectory.

    • Jialiang Wang
    • , Dandan Li
    •  & Zhijun Wang
  • Article
    | Open Access

    Five New World mammarenaviruses (NWMs) enter cells via binding to human transferrin receptor 1 (hTfR1). Here, Hickerson et al. show that hTfR1 targeting antibodies partially protect hTfR1-transgenic mice from lethal NWM challenge via competition of anti-hTfR1 antibody and viral glycoprotein for hTfR1.

    • Brady T. Hickerson
    • , Tracy R. Daniels-Wells
    •  & Brian B. Gowen
  • Article
    | Open Access

    Nonribosomal peptide synthetases work with additional enzymes to synthesise secondary metabolites and therapeutics. Here, the authors explore bacillamide D synthesis and show the oxidase action is done while the intermediate is attached to the synthetase and replicate this with an oxidase bound synthetase for bioengineering applications.

    • Camille Marie Fortinez
    • , Kristjan Bloudoff
    •  & T. Martin Schmeing
  • Article
    | Open Access

    Zhang and Cui et al. present in situ cryoEM structures of the trimeric spike of cytoplasmic polyhedrosis virus in both open and close conformations, and demonstrate that spike detachment from the capsid is triggered by the presence of SAM and ATP.

    • Yinong Zhang
    • , Yanxiang Cui
    •  & Z. Hong Zhou
  • Article
    | Open Access

    Aerobic energy metabolism is driven by proton-pumping respiratory supercomplexes. The study reports the structural basis for energy conversion in such supercomplex. It may aid metabolic engineering and drug design against diphtheria and tuberculosis.

    • Wei-Chun Kao
    • , Claire Ortmann de Percin Northumberland
    •  & Carola Hunte
  • Article
    | Open Access

    The plant biomass is a composite formed by a variety of polysaccharides and an aromatic polymer named lignin. Here, the authors use solid-state NMR spectroscopy to unveil the carbohydrate-aromatic interface that leads to the variable architecture of lignocellulose biomaterials.

    • Alex Kirui
    • , Wancheng Zhao
    •  & Tuo Wang
  • Article
    | Open Access

    The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression.

    • Anushweta Asthana
    • , Parameshwaran Ramanan
    •  & Seth M. Rubin
  • Article
    | Open Access

    The Kir potassium channels are known to operate and gate without a major conformational change. Here, the authors identify the permeation gate of Kir channels as a steric plug within the conduction pathway, describing how tightly associated anionic lipids pushing into fenestrations in the pore walls engage with the plug to operate the gate.

    • Ruitao Jin
    • , Sitong He
    •  & Jacqueline M. Gulbis
  • Article
    | Open Access

    The human microtubule nucleator γ-TuRC is composed of more than thirty subunits, including actin. Here the authors reveal the structural mechanism of modular γ-TuRC assembly and show a functional role of actin in microtubule nucleation.

    • Martin Würtz
    • , Erik Zupa
    •  & Stefan Pfeffer
  • Article
    | Open Access

    RAF kinases are essential for RAS protein signalling but how RAS binding regulates dimerization and activation of RAF has remained unclear. Here, the authors report cryoEM structures that provide mechanistic insights into the RAS-mediated monomer-to-dimer transition of full-length BRAF.

    • Juliana A. Martinez Fiesco
    • , David E. Durrant
    •  & Ping Zhang
  • Article
    | Open Access

    Melatonin receptors (MT1 and MT2) are the targets for melatonin, the major neurohormone involved in circadian rhythm and sleep regulation. Here the authors describe the structures of 2-iodomelatonin and ramelteon bound MT1–Gi and MT2-Gi, revealing that MT1 and MT2 possess distinctive features within the ligand-binding pocket.

    • Qinggong Wang
    • , Qiuyuan Lu
    •  & Yuyong Tao
  • Article
    | Open Access

    Properdin is the only known positive regulator of the human complement system, stabilising the convertase C3 in the alternative pathway of complement activation. Here, the authors report the identification and characterisation of a species-specific properdin inhibitor CirpA, derived from tick saliva.

    • Katharina Braunger
    • , Jiyoon Ahn
    •  & Susan M. Lea
  • Article
    | Open Access

    Ghrelin receptor regulates energy homeostasis through constitutive activity or by the ghrelin. Here the authors report two structures of ghrelin receptor bound to agonist and inverse agonist, providing insights into the mechanism of inverse agonism, which is of interest for specific ligand design.

    • Jiao Qin
    • , Ye Cai
    •  & Zhenhua Shao
  • Article
    | Open Access

    Prestin, expressed in outer hair cell (OHC), belongs to the Slc26 transporter family and functions as a voltage-driven motor that drives OHC electromotility. Here, the authors report cryo-EM structure and characterization of gerbil prestin, with insights into its mechanism of action.

    • Carmen Butan
    • , Qiang Song
    •  & Joseph Santos-Sacchi
  • Article
    | Open Access

    Influenza viruses carry their own RNAdependent RNA-polymerase that is highly conserved and a promising anti-viral target. Combining functional and structural data, Keown et al. characterise the inhibitory effect of nanobodies on 1918 pandemic H1N1 influenza strain polymerase complex and identify sensitive sites interfering with polymerase activity in vitro.

    • Jeremy R. Keown
    • , Zihan Zhu
    •  & Jonathan M. Grimes
  • Article
    | Open Access

    The authors show that the mechanism of BAK activation in mitochondrial apoptosis involves cooperation between direct activation by BH3-only protein BID and BAK autoactivation, providing a unifying basis for BAK triggering by BH3 ligands.

    • Geetika Singh
    • , Cristina D. Guibao
    •  & Tudor Moldoveanu
  • Article
    | Open Access

    Riboswitches contain an aptamer domain that recognizes a metabolite and an expression platform that regulates gene expression. Here the authors report the crystal structure of a preQ1-sensing riboswitch from Carnobacterium antarcticus that shows two metabolites in a single binding pocket.

    • Griffin M. Schroeder
    • , Chapin E. Cavender
    •  & Joseph E. Wedekind
  • Article
    | Open Access

    Pseudomonas aeruginosa employs lectins to bind to its host cells, and is known to be the major cause of lung infections. Lectin B (LecB) from Pseudomonas aeruginosa binds specifically to galactose and fucose and is important for pathogenicity, adhesion and biofilm formation. In this work, the neutron crystal structure (1.9 Å) of the deuterated LecB/Ca/fucose complex is reported. The structure, in combination with perdeuteration of the ligand and the receptor allowed the observation of hydrogen atoms, protonation states and hydrogen bonds involved in the interaction between pathogenic bacteria and host cells. Thus the study provides structural insights into the mechanism of high affinity binding of LecB to its targets.

    • Lukas Gajdos
    • , Matthew P. Blakeley
    •  & Anne Imberty