Structural biology articles within Nature Communications

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  • Article
    | Open Access

    TRPV6 is a calcium-selective ion channel that is involved in numerous calcium-dependent physiological processes and it is of interest as a potential drug target. Here, the authors present the cryo-EM structures of human TRPV6 with the bound inhibitors ruthenium red and the antifungal drug econazole and discuss their inhibition mechanisms.

    • Arthur Neuberger
    • , Kirill D. Nadezhdin
    •  & Alexander I. Sobolevsky

  • Article
    | Open Access

    Angiopoietin (Angpt)-Tie receptor 2 (Tie2) regulates vascular stability and is thus a potential therapeutic target in vascular diseases. Here, the authors report a Tie2-agonistic antibody which targets a site distinct from the Angpt 1-binding site and which influences Tie2 clustering and activation in an Angpt2 inhibition-resistant manner.

    • Gyunghee Jo
    • , Jeomil Bae
    •  & Ho Min Kim

  • Article
    | Open Access

    The Clostridium difficile virulence factors TcdA and TcdB contain a glucosyltransferase domain (GTD), which has both glucohydrolase (GH) and glucosyltransferase (GT) activities. Here, the authors characterize the transition state features of the TcdA and TcdB GH reactions by measuring kinetic isotope effects and they identify two transition state analogues, isofagomine and noeuromycin that inhibit TcdA and TcdB. They also present the crystal structures of TcdB-GTD bound to these inhibitors and the reaction product UDP.

    • Ashleigh S. Paparella
    • , Briana L. Aboulache
    •  & Vern L. Schramm

  • Article
    | Open Access

    The calcium binding protein S100B is an abundantly expressed protein in the brain and has neuro-protective functions by inhibiting Aβ aggregation and metal ion toxicity. Here, the authors combine cell biology and biochemical experiments with chemical kinetics and NMR measurements and show that S100B protein is an extracellular Tau chaperone and further characterize the interactions between S100B and Tau.

    • Guilherme G. Moreira
    • , François-Xavier Cantrelle
    •  & Cláudio M. Gomes

  • Article
    | Open Access

    G51D mutation of α-synuclein (α-syn) causes a subset of familial Parkinson’s disease that is characterized by an early onset and rapid progression of the disease. Here, the authors present the cryo-EM structure of full-length G51D α-syn fibrils that is distinct from other known α-syn fibril structures, and they show that G51D fibrils can cross-seed wild-type (WT) α-syn and that these cross-seeded WT fibrils replicate the G51D fibril structure.

    • Yunpeng Sun
    • , Houfang Long
    •  & Cong Liu

  • Article
    | Open Access

    The rice Lsi1 aquaporin mediates uptake of silicic acid via the roots. Here the authors show the crystal structure of rice Lsi1 and characterize a unique five residue hydrophilic selectivity filter providing a structural basis for the highly selective activity of Lsi1 in Si uptake.

    • Yasunori Saitoh
    • , Namiki Mitani-Ueno
    •  & Michihiro Suga

  • Article
    | Open Access

    NaK is a bacterial non-selective cation channel. Here, the authors use solution NMR to show that selectivity filter (SF) in NaK is dynamic, with structural differences between the Na+ and K + -bound states. The conformation of the SF is communicated to the pore-lining helices similarly as in the K + -selective channels.

    • Adam Lewis
    • , Vilius Kurauskas
    •  & Katherine Henzler-Wildman

  • Article
    | Open Access

    Anagrelide, nauclefine and DNMDP induce apoptosis by forming complexes with phosphodiesterase 3A (PDE3A) and Schlafen 12 protein (SLFN12). Here, the authors present the cryo-EM structures of PDE3A-SLFN12 complexes with these compounds as molecular glues. Based on the complex structure, they developed an anagrelide analog that shows a higher potency in inducing apoptosis in cultured cells and also promotes tumor growth inhibition in tumor xenografts, which is of interest for cancer drug development.

    • Jie Chen
    • , Nan Liu
    •  & Xiaodong Wang

  • Article
    | Open Access

    Legionella pneumophila (LP) employs the metaeffector SidJ to suppress the toxicity of SdeA and other LP SidE effector family members by catalysing the glutamylation of the catalytic Glu residue. Here, the authors present the cryo-EM structures of SidJ in complex with SdeA in two different states, which together with mutagenesis analysis provide insights into the substrate recognition and the mechanism of protein glutamylation by SidJ.

    • Michael Adams
    • , Rahul Sharma
    •  & Sagar Bhogaraju

  • Article
    | Open Access

    The 20S particle is part of the 26S proteasome, but also exists as a free complex. Here, the authors outline signature activities of the 20S and combine chemical, structural, functional and proteomic assays to show that the 20S can degrade ubiquitin tags along with conjugated substrates.

    • Indrajit Sahu
    • , Sachitanand M. Mali
    •  & Michael H. Glickman

  • Article
    | Open Access

    The RNA polymerase L of arenaviruses is of interest for drug design and its activity is inhibited by the matrix protein Z. Here, the authors present the cryo-EM structure of the Machupo virus polymerase L in complex with matrix protein Z and discuss the inhibitory mechanism.

    • Jun Ma
    • , Shuangyue Zhang
    •  & Xinzheng Zhang

  • Article
    | Open Access

    Termination of eukaryotic RNA polymerase III (Pol III)-mediated transcription occurs when the polymerase reaches a stretch of four or more deoxythymidine nucleotides (poly-dT) on the non-template strand. Here, the authors present the 3.6 Å cryo-EM structure of a human Pol III pre-termination complex (PTC) that was assembled on a 7 dT-containing DNA template and discuss the mechanism of poly-dT-dependent transcription termination of Pol III.

    • Haifeng Hou
    • , Yan Li
    •  & Yanhui Xu

  • Article
    | Open Access

    LNK is a potent negative regulator of cytokine signaling implicated in blood cells proliferation. Here the authors present structures of the substrate recognition (SH2) domain of LNK in complex with phosphorylated motifs from JAK2 and EPOR; providing insight into its binding specificity and mode of action.

    • Rhiannon Morris
    • , Yaoyuan Zhang
    •  & Jeffrey J. Babon

  • Article
    | Open Access

    The SARS-CoV-2 spike (S) protein mediates viral entry by binding of its receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor and mutations of the S protein may have a great impact on virus transmissibility. Here, the authors characterize the interactions of six different SARS-CoV-2 RBD variants among them Alpha, Beta and Gamma and present crystal structures of these ACE2-RBD complexes.

    • Pengcheng Han
    • , Chao Su
    •  & Jianxun Qi

  • Article
    | Open Access

    To prevent unregulated complement activation, extracellular chaperones capture soluble precursors to the membrane attack complex (sMAC). Here, structural analysis of sMAC reveals how clusterin recognizes heterogeneous sMAC complexes and inhibits polymerization of complement protein C9.

    • Anaïs Menny
    • , Marie V. Lukassen
    •  & Doryen Bubeck

  • Article
    | Open Access

    Translesion Synthesis is a process that enables cells to overcome the deleterious effects of replication stalling caused by DNA lesions. Here the authors present a Cryo-EM structure of human Y-family DNA polymerase k (Pol k) bound to PCNA, P/T DNA and an incoming nucleotide; and propose a model for polymerase switching in which “carrier state” Pol k is recruited to PCNA.

    • Claudia Lancey
    • , Muhammad Tehseen
    •  & Alfredo De Biasio

  • Article
    | Open Access

    Here the authors identify PHF3 SPOC domain as a reader of the phosphorylated RNA polymerase II (Pol II) C-terminal domain. They show that PHF3 clusters with Pol II complexes in cells, drives phase separation of Pol II in vitro, and regulates neuronal gene expression and neuronal differentiation.

    • Lisa-Marie Appel
    • , Vedran Franke
    •  & Dea Slade

  • Article
    | Open Access

    The Yersinia outer protein J (YopJ) family of effectors, which are present in many plant and animal pathogens are non-canonical acetyltransferases that are activated by the eukaryote-specific cofactor inositol hexaphosphate (InsP6). Here, the authors combine X-ray crystallography, biochemical and functional analyses to characterise the structure and activation mechanism of the YopJ family effector PopP2 from the plant pathogen Ralstonia solanacearum and observe that InsP6 binding induces major conformational changes in PopP2 with a helix-to-strand fold-switching in its catalytic core.

    • Yao Xia
    • , Rongfeng Zou
    •  & Zhi-Min Zhang

  • Article
    | Open Access

    The P4 ATPase lipid flippases play a crucial role in membrane biogenesis. Here the authors report the structure of the monomeric P4B ATPase Neo1 in several states, clarifying the mechanism of substrate transport.

    • Lin Bai
    • , Bhawik K. Jain
    •  & Huilin Li

  • Article
    | Open Access

    Both ubiquitin and NEDD8 can be phosphorylated, but the biological role of NEDD8 phosphorylation remains unclear. Here, the authors identify similarities and differences of ubiquitin and NEDD8 phosphorylation, showing that phosphorylated NEDD8 has a distinct interactome and regulates HSP70 proteins.

    • Katrin Stuber
    • , Tobias Schneider
    •  & Martin Scheffner

  • Article
    | Open Access

    Movement of the ribosome along an mRNA requires the universally-conserved translocase (EF-G in bacteria) that couples GTP hydrolysis to directed movement. Here the authors use time-resolved Cryo-EM to visualize the GTPase-powered step on native translocating ribosomes and capture key translocation intermediates.

    • Valentyn Petrychenko
    • , Bee-Zen Peng
    •  & Niels Fischer

  • Article
    | Open Access

    ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidenephosphatidylethanolamine (N-Ret-PE) to the cytoplasmic leaflet of photoreceptor membranes. ABCA4 mutations are associated with loss of vision. Here, structures of ABCA4 with and without substrate bound provide insight into N-Ret-PE binding and suggest a lateral access mechanism.

    • Jessica Fernandes Scortecci
    • , Laurie L. Molday
    •  & Robert S. Molday

  • Article
    | Open Access

    The gastric H+,K+-ATPase is a proton pump that creates the acidic environment of the stomach lumen, maintaining high proton gradient across the gastric mucosa cell membrane. Here, structural analysis of rationally designed H+,K+-ATPase mutants provides insight into this and other P-type ATPases cation binding stoichiometry and mechanisms.

    • Kazuhiro Abe
    • , Kenta Yamamoto
    •  & Atsunori Oshima

  • Article
    | Open Access

    The TOM and TIM23 complexes facilitate the transport of nuclear-encoded proteins into the mitochondrial matrix. Here, the authors use a stalled client protein to purify the translocation supercomplex and gain insight into the TOM-TIM23 interface and the mechanism of protein handover from the TOM to the TIM23 complex.

    • Ridhima Gomkale
    • , Andreas Linden
    •  & Peter Rehling

  • Article
    | Open Access

    Ufmylation is a well-established ubiquitin-like protein modification, but its mechanism is largely unclear. Here, the authors present a crystal structure of the ufmylation-specific E1-E2 complex, revealing differences to the ubiquitination machinery and mechanistic details of the ufmylation process.

    • Manoj Kumar
    • , Prasanth Padala
    •  & Reuven Wiener

  • Article
    | Open Access

    Biofilm formation in Bacillus subtilis requires expression of matrix production genes, which are upregulated by transcriptional activator RemA. Here, the authors show that RemA forms octameric rings with the potential to form a 16-meric superstructure, suggesting that the protein can wrap DNA through a LytTR-related domain.

    • Tamara Hoffmann
    • , Devid Mrusek
    •  & Gert Bange

  • Article
    | Open Access

    Mutations within subunits of the tRNA splicing endonuclease complex (TSEN) are associated with pontocerebellar hypoplasia (PCH). Here the authors show that tRNA intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers, and provide evidence that modulation of TSEN stability may contribute to PCH phenotypes.

    • Samoil Sekulovski
    • , Pascal Devant
    •  & Simon Trowitzsch

  • Article
    | Open Access

    The mechanisms involved in SLC4-mediated ion transport are still under debate. Here, the authors present a cryoEM structure of the Sodium-driven Chloride/Bicarbonate Exchanger NDCBE, which - together with computational modeling and mutagenesis - reveals molecular determinants of ion transport by SLC4.

    • Weiguang Wang
    • , Kirill Tsirulnikov
    •  & Ira Kurtz

  • Article
    | Open Access

    Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope in the receptor-binding domain of SARS-CoV-2 spike that is well conserved and show that these Abs can neutralize several variants of concerns.

    • Tingting Li
    • , Wenhui Xue
    •  & Ningshao Xia

  • Article
    | Open Access

    Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.

    • Jiandong Huo
    • , Halina Mikolajek
    •  & Raymond J. Owens

  • Article
    | Open Access

    In Saccharomyces cerevisiae, unchecked proliferation of Ty1 retrotransposons is controlled by the process of copy number control (CNC), which requires the p22/p18 protein, translated from an internal transcript within the Ty1 GAG gene. Here, the authors present the 2.8 Å crystal structure of a minimal p18 from Ty1-Gag that is able to restrict Ty1 transposition and identify two dimer interfaces in p18, whose roles were probed by mutagenesis both in vitro and in vivo. As p22/p18 contains only one of two conserved domains required for retroelement Gag assembly, they propose that p22/p18-Gag interactions block the Ty1 virus-like particle assembly pathway, resulting in defective particles incapable of supporting retrotransposition.

    • Matthew A. Cottee
    • , Sean L. Beckwith
    •  & Ian A. Taylor

  • Article
    | Open Access

    C. elegans piRNA biogenesis and chromosome segregation (PICS) complex is composed of TOFU-6, PICS-1, ERH-2, and two mutually exclusive factors PID-1 and TOST-1. By employing biochemical, structural, and cellular biology methods, the authors show that the PICS complex is an octamer consisting of two copies of each subunit, and functions in piRNA biogenesis and mitosis.

    • Xiaoyang Wang
    • , Chenming Zeng
    •  & Chao Xu

  • Article
    | Open Access

    Epistasis plays an important role in the evolution of novel protein functions because it determines the mutational path a protein takes. Here, the authors combine functional, structural and biophysical analyses to characterize epistasis in a computationally redesigned ligand-inducible allosteric transcription factor and found that epistasis creates distinct biophysical and biological functional landscapes.

    • Kyle K. Nishikawa
    • , Nicholas Hoppe
    •  & Srivatsan Raman

  • Article
    | Open Access

    Replicative hexameric helicases are fundamental components of replisomes. Here the authors resolve a cryo-EM structure of the E1 helicase from papillomavirus bound to a DNA replication fork, providing insights into the mechanism of DNA unwinding by these hexameric enzymes.

    • Abid Javed
    • , Balazs Major
    •  & Elena V. Orlova

  • Article
    | Open Access

    Here, the authors present a hierarchical disorder model for the analysis of disorder in both crystal and cryo-EM structures. They apply their approach to several structures of three proteins, including SARS-CoV-2 proteins, and discuss mechanistic and dynamical implications.

    • Nicholas M. Pearce
    •  & Piet Gros

  • Article
    | Open Access

    Understanding the structural basis for the inhibition of archaeal eukaryotic-like RNA polymerases (RNAPs) during virus infection is of interest for drug design. Here, the authors present the cryo-EM structures of apo Sulfolobus acidocaldarius RNAP and the RNAP complex structures with two regulatory factors, RIP and TFS4 that inhibit transcription and discuss their inhibitory mechanisms.

    • Simona Pilotto
    • , Thomas Fouqueau
    •  & Finn Werner

  • Article
    | Open Access

    Here, cryo-EM reconstructions of human cytomegalovirus (HCMV) virions reveal host tRNAs associated with the virion’s capsid-bound tegument protein, pp150. tRNA recruitment is mediated by the interactions specific for HCMV only, suggesting the explanation for the absence of such tRNA densities in related herpesviruses.

    • Yun-Tao Liu
    • , David Strugatsky
    •  & Z. Hong Zhou

  • Article
    | Open Access

    Soluble guanylate cyclase (sGC) is a validated drug target for cardiovascular diseases. Here, the authors report structures of human sGC in complex with NO and sGC stimulators or activator, providing insight into the mechanism of sGC activation by pharmacological compounds.

    • Rui Liu
    • , Yunlu Kang
    •  & Lei Chen

  • Article
    | Open Access

    Volume-regulated anion channels (VRACs) are heteromers of LRRC8 proteins, all containing the obligatory subunit LRRC8A. Here, the authors develop and characterize nanobodies that bind LRRC8A and allosterically modulate the function of homomeric LRRC8A and endogenous heteromeric channels, hinting at functional mechanisms present in VRACs.

    • Dawid Deneka
    • , Sonja Rutz
    •  & Raimund Dutzler

  • Article
    | Open Access

    OqxB is an RND (Resistance-Nodulation-Division) transporter that contributes to the antibiotic resistance in Klebsiella pneumoniae. Here, the authors report structural and functional characterization of OqxB, with insights into its substrate binding pocket and the role in fluoroquinolone resistance.

    • Nagakumar Bharatham
    • , Purnendu Bhowmik
    •  & Satoshi Murakami

  • Article
    | Open Access

    Dynamin mediates the fission of vesicles during endocytosis. Here, the authors report the cryoEM structure of a super-constricted two-start dynamin 1 filament- one of the two known helical forms of dynamin, with insights into the molecular mechanisms of dynamin-mediated membrane scission.

    • Jiwei Liu
    • , Frances Joan D. Alvarez
    •  & Peijun Zhang

  • Article
    | Open Access

    The large and small subunits of the ribosome are synthesized independently within the nucleolus — a membrane-less compartment within the nucleus — before being exported into the cytoplasm. Here, the authors use in situ cryo-ET to observe ribosome maturation and reveal the native organization of the nucleolus.

    • Philipp S. Erdmann
    • , Zhen Hou
    •  & Wolfgang Baumeister

  • Article
    | Open Access

    Bacteria adjust the expression of some of their metabolic enzymes through metabolite-sensing ribosome nascent chain complexes. Here the authors present a cryo-EM structure of an E. coli ribosome stalled during translation of the TnaC leader peptide and propose a model for L-Trp dependent ribosome stalling where L-Trp competes with release factor 2 for binding to the TnaC-ribosome complex.

    • Anne-Xander van der Stel
    • , Emily R. Gordon
    •  & C. Axel Innis

  • Article
    | Open Access

    The assembly of branched actin networks depends on the heterodimeric capping protein CP/CapZ. Combining cryoEM, in vitro reconstitution and cell biological assays, the authors show that CP not only prevents actin filament elongation but also selectively masks actin filament ends to promote nucleation.

    • Johanna Funk
    • , Felipe Merino
    •  & Peter Bieling

  • Article
    | Open Access

    Borosins are ribosomally encoded and posttranslationally modified peptide (RiPP) natural products featuring amide-backbone α-N-methylation. Here, the authors report the discovery and characterization of type IV borosin ‘split’ pathways encoding distinct, separate α-N-methyltransferases and precursor peptide substrates.

    • Fredarla S. Miller
    • , Kathryn K. Crone
    •  & Michael F. Freeman

  • Article
    | Open Access

    The endoplasmic-reticulum aminopeptidase ERAP1 processes peptides for antigen presentation. Here, the authors assess ERAP1 conformational states in solution, providing insight into the molecular mechanisms of ERAP1 substrate-length dependent catalytic activity and regulation, including the effects of autoimmune disease-associated polymorphism.

    • Zachary Maben
    • , Richa Arya
    •  & Lawrence J. Stern

  • Article
    | Open Access

    Here, the authors use solid-state NMR and EPR measurements to characterise the ATP hydrolysis transition state of the oligomeric bacterial DnaB helicase from Helicobacter pylori, which was trapped by using aluminium fluoride as a chemical mimic. They identify protein protons that coordinate to the phosphate groups of ADP and DNA and observe that the aluminium fluoride unit is highly mobile and fast-rotating.

    • Alexander A. Malär
    • , Nino Wili
    •  & Thomas Wiegand

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