Structural biology articles within Nature Communications

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  • Article
    | Open Access

    Previously, a broadly neutralizing antibody, 3I14, active against groups 1 and 2 influenza A viruses was isolated from human memory B cells and showed protection in mice from lethal viral challenge. Here, Harshbarger and Deming et al. provide the crystal structure of 3I14 Fab in complex with H3, H6, and H10.

    • Wayne D. Harshbarger
    • , Derrick Deming
    •  & Wayne A. Marasco

  • Article
    | Open Access

    TNF can be inhibited by small molecules that stabilize the TNF trimer in an asymmetric conformation. Here, the authors develop a monoclonal antibody that selectively binds this inactive form of TNF, enabling both target engagement assessment and structural characterization of TNF binding to TNF receptor 1.

    • Daniel J. Lightwood
    • , Rebecca J. Munro
    •  & Alastair D. G. Lawson

  • Article
    | Open Access

    Small molecules stabilising a distorted TNF trimer can inhibit TNF signaling, but the underlying mechanism is unclear. Here, the authors characterize the inhibitor-bound TNF-receptor complex structurally and biochemically, showing that the inhibitors alter TNF-receptor binding stoichiometry and cluster formation.

    • David McMillan
    • , Carlos Martinez-Fleites
    •  & James O’Connell

  • Article
    | Open Access

    Ribosomal RNA (rRNA) expression is regulated at the initiation stage of RNA synthesis. Here, the authors report cryo-EM structures of E. coli RNA polymerase and rRNA promoter complex with DksA/ppGpp on the way to open complex formation, identifying key steps in promoter recognition and opening.

    • Yeonoh Shin
    • , M. Zuhaib Qayyum
    •  & Katsuhiko S. Murakami

  • Article
    | Open Access

    The SARS-CoV-2 papain-like protease (PLpro) is of interest as a drug target. Here, the authors identify GRL0617 as a PPI (protein–protein interaction) inhibitor of SARS-CoV-2 PLpro that inhibits its deISGylating activity and present the mechanism of action of the compound through the GRL0617-bound PLpro crystal structure and NMR studies.

    • Ziyang Fu
    • , Bin Huang
    •  & Hao Huang

  • Article
    | Open Access

    Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating but the mechanisms regulating their localization and function are poorly understood. Here authors report a cryo-EM reconstruction of a three-headed axonemal dynein natively bound to doublet microtubules isolated from cilia which provides a framework to understand the roles of individual subunits.

    • Travis Walton
    • , Hao Wu
    •  & Alan Brown

  • Article
    | Open Access

    The tumor suppressor p53 is a master regulator of cellular stress response pathways, including cell cycle arrest and apoptosis. Here, the authors identify molecular mechanisms of p53 binding to high- and low-affinity p53 response elements in the genome, linked to cell cycle arrest and pro-apoptotic genes, respectively.

    • Marina Farkas
    • , Hideharu Hashimoto
    •  & Steven B. McMahon

  • Article
    | Open Access

    The Legionella effector DrrA AMPylates the host protein Rab1 during infection, but the mechanism is still under debate. Here, the authors provide structural insights into the low-affinity DrrA:Rab1 interaction, showing that Rab1 allosterically activates DrrA through a non-conventional binding mechanism.

    • Jiqing Du
    • , Marie-Kristin von Wrisberg
    •  & Aymelt Itzen

  • Article
    | Open Access

    SRSF1 is an oncoprotein that plays important roles in RNA metabolism. We reveal the structure of the human SRSF1 RRM1 bound to RNA, and propose a bimodal mode of interaction of the protein with RNA. A single mutation in RRM1 changed SRSF1 specificity for RNA and made it active on SMN2 exon7 splicing.

    • Antoine Cléry
    • , Miroslav Krepl
    •  & Frédéric H.-T. Allain

  • Article
    | Open Access

    Peptide-based filamentous assemblies are successfully used for generation of structurally ordered materials, but their de novo design and structural characterization is challenging. Here, the authors provide a strategy for the design of self-assembling peptide nanotubes based on modifications of an arginine clasp interaction motif, and report the cryo-EM structures of seven designed nanotubes.

    • Fengbin Wang
    • , Ordy Gnewou
    •  & Vincent P. Conticello

  • Article
    | Open Access

    Plants regulate phosphate homeostasis via the interaction of PHR transcription factors with SPX receptors bound to inositol pyrophosphate signaling molecules. Here the authors show that inositol pyrophosphate-bound SPX interacts with the coiled-coil domain of PHR, which regulates the oligomerization and activity of the transcription factor.

    • Martina K. Ried
    • , Rebekka Wild
    •  & Michael Hothorn

  • Article
    | Open Access

    Family 1 glycosidases (GH1) are present in the three domains of life and share classical TIM-barrel fold. Structural and biochemical analyses of a resurrected ancestral GH1 enzyme reveal heme binding, not known in its modern descendants. Heme rigidifies the TIM-barrel and allosterically enhances catalysis.

    • Gloria Gamiz-Arco
    • , Luis I. Gutierrez-Rus
    •  & Jose M. Sanchez-Ruiz

  • Article
    | Open Access

    RAD51 and DMC1 recombinases catalyse high-fidelity and mismatch tolerant recombination, processes that are indispensable for the maintenance of genomic integrity. Here, the authors via cryo-EM, molecular dynamics simulation and functional analysis elucidate the structural difference between RAD51 and DMC1 with regard to mismatch tolerance.

    • Shih-Chi Luo
    • , Hsin-Yi Yeh
    •  & Ming-Daw Tsai

  • Article
    | Open Access

    The E2-like enzyme human Atg3 catalyses the transfer of ubiquitin-like mammalian LC3 to the lipid phosphatidylethanolamine during autophagosome formation. Here, the authors combine NMR measurements with in vitro biochemical and in vivo cellular assays and show that the N-terminal conserved region of human Atg3 communicates information from the curvature-sensing domain to its active site.

    • Yansheng Ye
    • , Erin R. Tyndall
    •  & Fang Tian

  • Article
    | Open Access

    Lipopolysaccharides, important components of the bacterial cell envelope, are synthesized at the inner membrane by the Wzx/Wzy-dependent assembly pathway. A cryo-EM structure of an intact E. coli WzzB, the polysaccharide co-polymerase component of this pathway, reveals details of the transmembrane, cytoplasmic domains and a conserved a proline-rich segment proximal to the C-terminal transmembrane helix.

    • Benjamin Wiseman
    • , Ram Gopal Nitharwal
    •  & Martin Högbom

  • Article
    | Open Access

    The GABARAP protein is known to support the stability of GABAA receptors (GABAARs) in synapses, but the underlying molecular mechanisms remained to be elucidated. Here authors use biochemistry, X-ray crystallography and electrophsyiology and show that GABARAP directly binds to a previously unappreciated region in the γ2 subunit of GABAAR.

    • Jin Ye
    • , Guichang Zou
    •  & Chao Wang

  • Article
    | Open Access

    Mass spectrometry-based covalent labeling techniques such as hydroxyl radical protein footprinting (HRPF) provide information about protein tertiary structures. Here, the authors present a dynamics driven HRPF-guided algorithm for protein structure prediction that is incorporated in the Rosetta software suite and only requires the protein sequence and HRPF data as input and they demonstrate its successful application to four benchmark proteins.

    • Sarah E. Biehn
    •  & Steffen Lindert

  • Article
    | Open Access

    Remdesivir is a nucleoside analog that inhibits the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and is used as a drug to treat COVID19 patients. Here, the authors provide insights into the mechanism of remdesivir-induced RdRp stalling by determining the cryo-EM structures of SARS-CoV-2 RdRp with bound RNA molecules that contain remdesivir at defined positions and observe that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation.

    • Goran Kokic
    • , Hauke S. Hillen
    •  & Patrick Cramer

  • Article
    | Open Access

    Rad5 is a hub connecting three replication stress tolerance pathways. Here, the authors present the 3.3 Å crystal structure of a N-terminal truncated K.lactis Rad5 construct that reveals the spatial arrangement of the HIRAN, Snf2 and RING domains and structure-guided in vitro and in vivo experiments reveal multiple activities of the yeast Rad5 HIRAN domain among them a role in binding PCNA and supporting its ubiquitination.

    • Miaomiao Shen
    • , Nalini Dhingra
    •  & Song Xiang

  • Article
    | Open Access

    Nonribosomal lipopeptides contain an acyl chain important for bioactivity, but its incorporation into the peptidyl backbone, mediated by the starter condensation (Cs) domain of nonribosomal peptide synthases, is not fully understood. Here, the authors show that acyl chains of different lengths can be obtained by engineering Cs domains and identify residues that determine the selectivity for acyl chains.

    • Lin Zhong
    • , Xiaotong Diao
    •  & Xiaoying Bian

  • Article
    | Open Access

    Tuberous sclerosis complex (TSC) regulates cell growth by controlling the activity of mTORC1. The structure of human TSC complex reveals an arch-shaped, asymmetric architecture and a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7 subunits and suggests a mechanism by which TSC2 accelerates GTP hydrolysis against a small GTPase Rheb.

    • Huirong Yang
    • , Zishuo Yu
    •  & Yanhui Xu

  • Article
    | Open Access

    Infection by Helicobacter pylori is associated with peptic ulcers and gastric cancer. H. pylori urease is required for colonization of the stomach and thus an attractive antimicrobial drug target. Cryo-EM analyses of the H. pylori urease with inhibitors bound reveal structural details useful in rational drug design.

    • Eva S. Cunha
    • , Xiaorui Chen
    •  & Hartmut Luecke

  • Article
    | Open Access

    Here, the authors identify and characterize two mouse-derived monoclonal antibodies against SARS-CoV-2 spike protein that target different epitopes in RBD and block the interaction S/ACE2 and show that a formulated humanized version cocktail exhibits prophylaxis and therapeutic antiviral effects in an hACE2-adenovector expressed mouse model.

    • Chao Zhang
    • , Yifan Wang
    •  & Zhong Huang

  • Article
    | Open Access

    SARS-CoV-2 S protein prematurely refolds to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yield. Here, Juraszek et al. present a stable SARS-CoV-2 S-closed protein variant with increased expression and correct folding, predominantly in closed prefusion conformation.

    • Jarek Juraszek
    • , Lucy Rutten
    •  & Johannes P. M. Langedijk

  • Article
    | Open Access

    Dual oxidases (DUOXs), assembled from the catalytic DUOX and the auxiliary DUOXA subunits, produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen in a calcium-activated manner. Here authors report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states.

    • Jing-Xiang Wu
    • , Rui Liu
    •  & Lei Chen

  • Article
    | Open Access

    Pathogen triggered N-terminal degradation of NLRP1 and CARD8 by the proteasome releases their C-terminal UPA-CARD fragments (CT) to form the inflammasome, which in turn activates caspase-1. Here, the authors present the cryo-EM structures of the NLRP1-CT and CARD8-CT helical filaments as well as the ASC−caspase-1 octamer structure, which together with in vitro and cell based assays provide further insights into the architecture and specificity of the active NLRP1 and CARD8 inflammasomes.

    • L. Robert Hollingsworth
    • , Liron David
    •  & Hao Wu

  • Article
    | Open Access

    The bifunctional enzyme CoaBC catalyses the second and third step in the Coenzyme A (CoA) biosynthesis pathway and is of interest as a M. tuberculosis drug target. Here, the authors present the full-length crystal structure of Mycobacterium smegmatis CoaBC, which is regulated by CoA and CoA thioesters and forms a dodecamer and by performing a high-throughput screen they identify selective inhibitors of M. tuberculosis CoaB that bind to an allosteric site within CoaB.

    • Vitor Mendes
    • , Simon R. Green
    •  & Tom L. Blundell

  • Article
    | Open Access

    NLRP1 and CARD8 are two recently described sensor proteins for the human inflammasome complex. Here, the authors present the cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains, which reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. They further propose a two-step model for NLRP1 activation.

    • Qin Gong
    • , Kim Robinson
    •  & Bin Wu

  • Article
    | Open Access

    The spike protein of coronaviruses (S-protein) is an envelope-anchored trimeric type I transmembrane glycoprotein that mediates receptor binding and the fusion of the viral and host cell membranes. Here the authors report the conformational states of HCoV-229E S trimer and observe the conformational changes in S1 subunit from closed state to activated state for receptor binding.

    • Xiyong Song
    • , Yuejun Shi
    •  & Guiqing Peng

  • Article
    | Open Access

    The small proton-coupled transporter EmrE confers multidrug resistance in bacteria. The structure of drug-bound EmrE in phospholipid bilayers is now determined using solid-state NMR. The structure provides detailed insights into the molecular mechanism of substrate recognition by this transporter.

    • Alexander A. Shcherbakov
    • , Grant Hisao
    •  & Mei Hong

  • Article
    | Open Access

    Structural and functional analysis of mitochondria from the human parasite Toxoplasma gondii reveals that its ATP synthase assembles into cyclic hexamers, arranged together in a form of pentagonal pyramids required for maintenance of cristae morphology in Apicomplexa.

    • Alexander Mühleip
    • , Rasmus Kock Flygaard
    •  & Alexey Amunts

  • Article
    | Open Access

    The human AAA+protein p97 plays an important role in cellular protein homeostasis. Here, the authors use cryo-EM to obtain further insights into how p97 interacts with its co-factor Npl4 and they observe three distinct conformational states of Npl4 in complex with human p97, which suggests that a seesaw motion is essential for the unfolding activity of the p97 complex.

    • Man Pan
    • , Qingyun Zheng
    •  & Minglei Zhao

  • Article
    | Open Access

    In Bacteroidetes, SusCD complexes mediate uptake of large nutrients across the outer membrane. SusCD structures in the apo state and in complex with β2,6 fructo-oligosaccharides reveal several substrate molecules in the binding cavity and suggest details of the pedal bin mechanism employed in glycan import.

    • Declan A. Gray
    • , Joshua B. R. White
    •  & Bert van den Berg

  • Article
    | Open Access

    The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac NaV1.5 channels. Here authors reveal the cryo-EM structure of LqhIII bound to NaV1.5 which shows that LqhIII traps the gating charges of the S4 segment in a unique intermediate-activated state and explains why LqhIII slows inactivation of NaV channels but does not open them.

    • Daohua Jiang
    • , Lige Tonggu
    •  & William A. Catterall

  • Article
    | Open Access

    The SOX2 pioneer transcription factor performs critical roles in pluripotency and self-renewal of embryonic stem cells. Here the authors show that SOX2’s two nuclear localization signal sequences form a contiguous binding interface on the nuclear import receptor importin-α3, and provide a structural basis for the preference of SOX2 binding to IMPα3.

    • Bikshapathi Jagga
    • , Megan Edwards
    •  & Jade K. Forwood

  • Article
    | Open Access

    In most model yeast species the Origin Recognition Complex (ORC) binds defined and species-specific base sequences while in humans what determines the binding appears to be more complex. Here the authors reveal that the yeast’s ORC complex binding specificity is dependent on a 19-amino acid insertion helix in the Orc4 subunit which is lost in human.

    • Clare S. K. Lee
    • , Ming Fung Cheung
    •  & Bik-Kwoon Tye

  • Article
    | Open Access

    The dopamine D2 receptor (D2R) is a GPCR and an important drug target for schizophrenia treatment. Here, the authors present the crystal structure of human D2R in complex with the antipsychotic drug spiperone, which is of interest for designing antipsychotics with improved receptor selectivity.

    • Dohyun Im
    • , Asuka Inoue
    •  & Tatsuro Shimamura

  • Article
    | Open Access

    The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Here, authors report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging.

    • Florian Fäßler
    • , Georgi Dimchev
    •  & Florian K. M. Schur

  • Article
    | Open Access

    The authors present a method for calculating the accuracy of an NMR structure, where flexibility from backbone chemical shifts is compared to structural flexibility predicted using rigidity theory. The authors validate their method and use it to compare the accuracy of NMR and X-ray structures.

    • Nicholas J. Fowler
    • , Adnan Sljoka
    •  & Mike P. Williamson

  • Article
    | Open Access

    The bacterial helicase-like transcription factor HelD associates with the RNA polymerase (RNAP) and recycles stalled transcription complexes. Here, the authors present the cryo-EM structures of three Mycobacterium smegmatis HelD bound RNAP complexes and further show that HelD can prevent the binding of the RNAP core to non-specific DNA and also actively removes RNAP from stalled elongation complexes.

    • Tomáš Kouba
    • , Tomáš Koval’
    •  & Libor Krásný

  • Article
    | Open Access

    The bacterial helicase-like transcription factor HelD interacts with the RNA polymerase (RNAP) and together with the RNAP δ subunit enhances RNAP cycling. Here, the authors present the cryo-EM structures of the monomeric and dimeric Bacillus subtilis RNAP-δ-HelD complexes and suggest a model for HelD/δ-mediated RNAP recycling and putative hibernation.

    • Hao-Hong Pei
    • , Tarek Hilal
    •  & Markus C. Wahl

  • Article
    | Open Access

    Gram-positive bacteria contain a transcription factor HelD that is able to remove and recycle stalled transcription complexes. Here the authors provide mechanistic insights into this process by determining the cryo-EM structures of the Bacillus subtilis RNA polymerase (RNAP) elongation complex and the RNAP-HelD transcription recycling complex and propose a model of HelD catalysed transcription recycling.

    • Timothy P. Newing
    • , Aaron J. Oakley
    •  & Peter J. Lewis

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