Structural biology articles within Nature Communications

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  • Article
    | Open Access

    KEOPS is an evolutionary conserved complex with a core of four core subunits—Pcc1, Kae1, Bud32 and Cgi121—that catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine (t6A). Here the authors describe a Cgi121-tRNA crystal structure and new composite model of the KEOPS holo-enzyme-substrate complex that shed light on the t6A catalytic cycle and its regulation.

    • Jonah Beenstock
    • , Samara Mishelle Ona
    •  & Frank Sicheri

  • Article
    | Open Access

    Most approaches for modeling the membrane protein complexes are not capable of incorporating the topological information provided by the membrane. Here authors present an integrative computational protocol for the modeling of membrane-associated protein assemblies, specifically complexes consisting of a membrane-embedded protein and a soluble partner.

    • Jorge Roel-Touris
    • , Brian Jiménez-García
    •  & Alexandre M. J. J. Bonvin

  • Article
    | Open Access

    The NALCN channel mediates sodium leak currents, which in turn adjusts resting membrane potential and neuronal excitability. Here the authors describe a cryo-EM structure of mammalian NALCN-FAM155A channel complex, showing how selectivity filter contributes to sodium permeation and calcium block and how the voltage sensors contribute to current modulation.

    • Yunlu Kang
    • , Jing-Xiang Wu
    •  & Lei Chen

  • Article
    | Open Access

    XylE is a bacterial xylose transporter and homologue of human glucose transporters GLUTs 1-4. HDX-MS, mutagenesis and MD simulations suggest that protonation of a conserved aspartate triggers conformational transition from outward- to inward facing state only in the presence of substrate xylose. In contrast, inhibitor glucose locks the transporter in the outward facing state.

    • Ruyu Jia
    • , Chloe Martens
    •  & Argyris Politis

  • Article
    | Open Access

    Immune cells express immunoproteasomes (i20S), which bind to specialized regulators, contain different catalytic subunits and generate immunogenic peptides. HDX-MS—based assessment of the differences between the conformational dynamics of standard and i20s reveals specific, allosteric changes in i20S and upon regulator binding.

    • Jean Lesne
    • , Marie Locard-Paulet
    •  & Julien Marcoux

  • Article
    | Open Access

    How clamp conformation is regulated in the transcription cycle of stalk-containing archaeal and eukaryotic RNA polymerase (RNAP) systems is still not well understood. Here, the authors combine cryo-EM, X-ray crystallography and photo-crosslinking assays to structurally characterise RNAP, the RNAP-TFEα binary and RNAP-TFEα-promoter DNA ternary complexes from the archaea Thermococcus kodakarensis and enables them to describe the dynamic conformational changes of the general transcription factor TFEα and RNAP during the early stage of transcription cycle.

    • Sung-Hoon Jun
    • , Jaekyung Hyun
    •  & Katsuhiko S. Murakami

  • Article
    | Open Access

    The SARS-CoV-2 viral genome is encapsulated by the nucleocapsid protein (NSARS-CoV-2) that is essential for viral replication. Here, the authors show that RNA induces liquid-liquid phase separation of NSARS-CoV-2 and how NSARS-CoV-2 phosphorylation modulates RNA-binding and phase separation and that these RNA/NSARS-CoV-2-droplets recruit and concentrate the SARS-CoV-2 RNA-dependent RNA polymerase complex in vitro, which would enable high initiation and elongation rates during viral transcription.

    • Adriana Savastano
    • , Alain Ibáñez de Opakua
    •  & Markus Zweckstetter

  • Article
    | Open Access

    Cyclophilin A (CypA) is a peptidylprolyl isomerase that also has chaperone activity and interacts with the intrinsically disordered protein α-Synuclein (aSyn). Here, the authors combine NMR measurements and biochemical experiments to characterise the interplay between the catalysis of proline isomerization and molecular chaperone activity of CypA and find that both activities have opposing effects on aSyn and further show that the that cis/trans isomerization outpowers the holding activity of CypA.

    • Filippo Favretto
    • , David Flores
    •  & Markus Zweckstetter

  • Article
    | Open Access

    Gdx-Clo is a bacterial transporter from the small multidrug resistance (SMR) family. Here, the authors use solid supported membrane electrophysiology to characterize Gdx-Clo functionally and report crystal structures of Gdx-Clo which confirm the dual topology architecture and offer insight into substrate binding and transport mechanism.

    • Ali A. Kermani
    • , Christian B. Macdonald
    •  & Randy B. Stockbridge

  • Article
    | Open Access

    Pathogenic IgA1 metalloproteases block the initial host immune response by cleaving host IgA1. Using cryoEM, the authors here provide structural insights into the substrate recognition mechanism of Streptococcus pneumoniae IgA1 protease, and develop a protease-inhibiting antibody.

    • Zhiming Wang
    • , Jeremy Rahkola
    •  & Elan Eisenmesser

  • Article
    | Open Access

    The Y complex is an essential component of the nuclear pore complex but a full model based on experimental structures is lacking. Here, the authors complete the model of the yeast Y complex with two nanobody-bound crystal structures, providing molecular insights into its flexibility and membrane anchoring.

    • Sarah A. Nordeen
    • , Daniel L. Turman
    •  & Thomas U. Schwartz

  • Article
    | Open Access

    Respiratory complex I plays a key role in energy metabolism. Cryo-EM structure of a mutant accessory subunit LYRM6 from the yeast Yarrowia lipolytica and molecular dynamics simulations reveal conformational changes at the interface between LYRM6 and subunit ND3, propagated further into the complex. These findings offer insight into the mechanism of proton pumping by respiratory complex I.

    • Etienne Galemou Yoga
    • , Kristian Parey
    •  & Heike Angerer

  • Article
    | Open Access

    In type I-D CRISPR–Cas systems, the nuclease and helicase activities are carried out by separate subunits. The crystal structure of Sulfolobus islandicus type I-D large subunit Cas10d, containing a nuclease domain, reveals unusual architecture. The structure of Cas10d in complex with anti-CRISPR protein AcrID1 suggests that the latter sequesters Cas10d in a nonfunctional state.

    • M. Cemre Manav
    • , Lan B. Van
    •  & Ditlev E. Brodersen

  • Article
    | Open Access

    EphA2 is the specific entry receptor for both human γ-herpesviruses Kaposi sarcoma associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). Here, the authors present the crystal structures of the EphA2 ligand binding domain (LBD) bound to the viral glycoprotein gHgL from EBV and KSHV and further analyse EphA2 gHgL interactions with mutagenesis experiments in cell-based fusion assays and suggest that other animal γ-herpesviruses could also use EphA2 as an entry receptor.

    • Chao Su
    • , Lili Wu
    •  & Jinghua Yan

  • Article
    | Open Access

    Cyclohexadienyl dehydratase (CDT) evolved from a cationic amino acid binding protein ancestor without enzymatic activity (AncCDT-1) via a series of intermediates. Here, the authors combine EPR, X-ray crystallography and MD simulations to study the structural dynamics of these evolutionary intermediates and observe that they predominantly populate catalytically unproductive conformations, while CDT exclusively samples catalytically relevant compact states, and which reveals how the conformational landscape changes along the evolutionary trajectory.

    • Joe A. Kaczmarski
    • , Mithun C. Mahawaththa
    •  & Colin J. Jackson

  • Article
    | Open Access

    Type I-C Cascade (the CRISPR-associated complex for antiviral defense) is a minimal system, comprising only three unique Cas proteins. Cryo-EM structure of the Desulfovibrio vulgaris type I-C Cascade reveals the molecular mechanisms that underlie RNA-directed complex assembly.

    • Roisin E. O’Brien
    • , Inês C. Santos
    •  & David W. Taylor

  • Article
    | Open Access

    The sulfur-reducing enzyme MBS and the hydrogen-gas evolving MBH are the evolutionary link between the ancestor Mrp antiporter and the mitochondrial respiratory complex I. Here, the authors characterise MBS from the hyperthermophilic archaeon Pyrococcus furiosus, solve its cryo-EM structure and discuss the structural evolution from Mrp to MBH and MBS and to the modern-day complex I.

    • Hongjun Yu
    • , Dominik K. Haja
    •  & Michael W. W. Adams

  • Article
    | Open Access

    The bacterial defense system McrBC is a two-component motor-driven nuclease complex that cleaves foreign DNA. Here, the authors present the structures of the GTP-specific AAA + motor protein McrB and two McrBC complexes and discuss the molecular mechanism of how McrC binding stimulates McrB GTP hydrolysis.

    • Yiming Niu
    • , Hiroshi Suzuki
    •  & Joshua S. Chappie

  • Article
    | Open Access

    For almost forty years, N-(1-pyrene) iodoacetamide has been used to label actin at C374, but the mechanisms of the fluorescence changes are still unknown due to the lack of structural information. Here authors provide cryo-EM structures of actin filaments with N-1-pyrene conjugated to cysteine 374 and either ADP or ADP-phosphate in the active site.

    • Steven Z. Chou
    •  & Thomas D. Pollard

  • Article
    | Open Access

    SARS-CoV-2 virus replication and transcription is mediated by the replication and transcription complex (RTC) that is composed of 16 non-structural proteins (nsp). Here, the authors present the cryo-EM structure of a SARS-CoV-2 mini RTC consisting of the viral RNA-dependent RNA polymerase with a template-primer RNA, the RdRp cofactors nsp7 and nsp8 and two nsp13 helicase molecules, and they propose a model for helicase-polymerase coupling during SARS-CoV-2 RTC assembly.

    • Liming Yan
    • , Ying Zhang
    •  & Zhiyong Lou

  • Article
    | Open Access

    The SARS-CoV-2 main protease (Mpro) is one of two cysteine proteases essential for viral replication. Here, the authors determine the crystal structure of an Mpro acyl intermediate with its native C-terminal autocleavage sequence and the structure of a product bound active site mutant (C145A), which are of interest for antiviral drug development.

    • Jaeyong Lee
    • , Liam J. Worrall
    •  & Natalie C. J. Strynadka

  • Article
    | Open Access

    Here the authors visualize SARS-CoV-2 infected cells by in situ cryo-electron tomography, delineating the structural organization and conformational changes that occur during virus replication and budding; and provide insight into vRNP architecture and RNA networks in double membrane vesicles.

    • Steffen Klein
    • , Mirko Cortese
    •  & Petr Chlanda

  • Article
    | Open Access

    NALCN, a sodium leak channel, plays a key role in regulating the resting membrane potential and controlling neuronal excitability. Here the authors report a cryo-EM structure of human NALCN in complex with FAM155A, that with complementary functional analyses provide insights on its ion selectivity, voltage sensing and specific interactions with auxiliary subunits.

    • Jiongfang Xie
    • , Meng Ke
    •  & Zhen Yan

  • Article
    | Open Access

    Cholesterol-dependent cytolysins (CDCs) are bacterial pore-forming virulence factors. Cryo-EM structure of an early conformation of the CDC ILY from Streptococcus intermedius, bound to the human immune receptor CD59, provides insight into ILY oligomerization and role of cholesterol in membrane lysis.

    • Nita R. Shah
    • , Tomas B. Voisin
    •  & Doryen Bubeck

  • Article
    | Open Access

    Bacteriophages of the Siphoviridae family have a long, flexible, non-contractile tail that has been difficult to characterize structurally. Here, the authors present the atomic structure of the tail tube of one of these phages, showing a hollow flexible tube formed by hexameric rings stacked by flexible linkers.

    • Maximilian Zinke
    • , Katrin A. A. Sachowsky
    •  & Adam Lange

  • Article
    | Open Access

    The ATF2 transcription factor is phosphorylated by different mitogen-activated protein (MAP) kinases. Here, the authors show that the functionally distinct MAP kinases JNK and p38 control ATF2 through different binding sites and differential phosphorylation, thereby modulating ATF2’s sensitivity to the JNK and p38 pathways.

    • Klára Kirsch
    • , András Zeke
    •  & Attila Reményi

  • Article
    | Open Access

    The main components of the prokaryotic chemotaxis system, chemoreceptors, organize into a hexagonal (P6 symmetry) extended array. Here authors use cryo-ET and report an alternative symmetry (P2) of the chemotaxis apparatus that emerges from a strict linear organization of the histidine kinase CheA in Treponema denticola cells.

    • Alise R. Muok
    • , Davi R. Ortega
    •  & Ariane Briegel

  • Article
    | Open Access

    The low-complexity (LC) domain mediates liquid-liquid phase separation and fibril formation of the RNA-binding protein FUS (FUsed in Sarcoma). Here, the authors combine cryo-EM, solid-state NMR measurements and MD simulations to structurally characterise the fibrils formed by the C-terminal half of the FUS LC domain and discuss stabilizing interactions within the fibril core.

    • Myungwoon Lee
    • , Ujjayini Ghosh
    •  & Robert Tycko

  • Article
    | Open Access

    High-throughput single particle cryo-EM, for instance in drug research, requires the automation of the single particle analysis workflow. Here, the authors present TranSPHIRE, a software package that allows the fully-automated, feedback-driven processing of cryo-EM datasets during data acquisition.

    • Markus Stabrin
    • , Fabian Schoenfeld
    •  & Stefan Raunser

  • Article
    | Open Access

    Activating adaptors that link dynein to its general cofactor dynactin recruit specific cargoes and regulate dynein’s activity and processive motility in retrograde transport. Here, the authors present the crystal structures of two adaptor complexes with the dynein light intermediate chain-1 (LIC1) and show that activating adaptors can be grouped into three structural classes based on their different interactions with LIC1.

    • In-Gyun Lee
    • , Sydney E. Cason
    •  & Roberto Dominguez

  • Article
    | Open Access

    Ferroportin is an iron exporter essential for releasing cellular iron into circulation and is inhibited by a peptide hormone, hepcidin. Here authors present cryo-EM structures of the ferroportin from the primate Philippine tarsier (TsFpn) with and without hepcidin and show that TsFpn is an electroneutral H+ /Fe2+ antiporter.

    • Yaping Pan
    • , Zhenning Ren
    •  & Ming Zhou

  • Article
    | Open Access

    So far only a few compounds have been reported as splicing modulators. Here, the authors combine high-throughput screening, chemical synthesis, NMR, X-ray crystallography with functional studies and develop phenothiazines as inhibitors for the U2AF Homology Motif (UHM) domains of proteins that regulate splicing and show that they inhibit early spliceosome assembly on pre-mRNA substrates in vitro.

    • Pravin Kumar Ankush Jagtap
    • , Tomáš Kubelka
    •  & Michael Sattler

  • Article
    | Open Access

    Rhodopsin phosphodiesterase (Rh-PDE) hydrolyzes both cAMP and cGMP in a light-dependent manner. Structural and functional analyses of the Rh-PDE from Salpingoeca rosetta reveal unusual rhodopsin topology comprising 8 transmembrane helices (TMs) and suggest that TM0 plays a crucial role in the enzymatic photoactivity.

    • Tatsuya Ikuta
    • , Wataru Shihoya
    •  & Osamu Nureki

  • Article
    | Open Access

    As protein synthesis takes place, newly synthesized polypeptide chain passes through the ribosomal exit tunnel, which can accommodate up to 70 residues in the case of a helical peptide. Here the authors show that oxidation of cysteine residues in the nascent chain can occur within the ribosome exit tunnel, where sufficient space exists for the formation of disulfide bonds.

    • Linda Schulte
    • , Jiafei Mao
    •  & Harald Schwalbe

  • Article
    | Open Access

    Here, the authors isolate several nanobodies from a synthetic library that bind the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) and neutralize S pseudotyped viruses. Cryo-EM structure of Spike with one nanobody and further biophysical analysis shows competition with ACE2 binding.

    • Tânia F. Custódio
    • , Hrishikesh Das
    •  & Christian Löw

  • Article
    | Open Access

    The structure and dynamics of large proteins and complexes can be studied by methyl-NMR but resonance assignment is still challenging. Here, the authors present a NMR method that leverages optimal control pulse design to unambiguously distinguish between Leu and Val using a simple 2D HMQC experiment and they apply it to several proteins including Cas9, interleukin, and human translation initiation factor eIF4a.

    • Soumya P. Behera
    • , Abhinav Dubey
    •  & Haribabu Arthanari

  • Article
    | Open Access

    Alternative rescue factor B (ArfB) is an enzyme that releases peptides from stalled ribosomes to allow ribosome recycling. Here the authors carry-out cryo-EM analyses of 70S ribosomes complexed with ArfB on either a short or longer mRNA to reveal distinct modes of ArfB function.

    • Christine E. Carbone
    • , Gabriel Demo
    •  & Andrei A. Korostelev

  • Article
    | Open Access

    β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for catabolism of trehalose and maltose. Coupled analyses of multiple βPGM structures and enzymatic activity lead to the proposal of allomorphy — a post-translational mechanism controlling enzyme activity.

    • Henry P. Wood
    • , F. Aaron Cruz-Navarrete
    •  & Jonathan P. Waltho

  • Article
    | Open Access

    The DNA helicase ASCC3 is the largest subunit of the activating signal co-integrator complex (ASCC), and its DNA unwinding activity is required for the AlkBH3/ASCC-dependent DNA de-alkylation repair pathway. Here, the authors identify a minimal stable complex of the two ASCC subunits ASCC2 and ASCC3, determine the complex crystal structure and further show that cancer-related mutations at the interface between both proteins reduce ASCC2–ASCC3 affinity.

    • Junqiao Jia
    • , Eva Absmeier
    •  & Markus C. Wahl

  • Article
    | Open Access

    The conserved eukaryotic heterotrimeric NatC complex co-translationally acetylates the N-termini of numerous target proteins. Here, the authors provide insights into the catalytic mechanism of NatC by determining the crystal structures of Saccharomyces cerevisiae NatC in the absence and presence of cofactors and peptide substrates and reveal the molecular basis of substrate binding by further biochemical analyses.

    • Stephan Grunwald
    • , Linus V. M. Hopf
    •  & Oliver Daumke

  • Article
    | Open Access

    Determining dynamic ensembles of biomolecules is still challenging. Here the authors present an approach for rapid RNA ensemble determination that combines RNA structure prediction tools and NMR residual dipolar coupling data and use it to determine atomistic ensemble models for a variety of RNAs.

    • Honglue Shi
    • , Atul Rangadurai
    •  & Hashim M. Al-Hashimi

  • Article
    | Open Access

    Human Microrchidia 4 (MORC4) ATPase has been implicated in acute and chronic pancreatitis, inflammatory disorders and cancer. Here the authors describe the structure–function relationship of MORC4 and define the molecular mechanism for MORC4 activation.

    • Adam H. Tencer
    • , Khan L. Cox
    •  & Tatiana G. Kutateladze

  • Article
    | Open Access

    AtaT is a type-II toxin from enterohemorrhagic E. coli, reported to acetylate the aminoacyl-moiety of initiator Met-tRNAfMet, thus inhibiting translation initiation. Biochemical analysis suggests that AtaT has a broader specificity for aminoacyl-tRNAs and inhibits global translation. Structure of AtaT in complex with acetylated Met-tRNAfMet offers insight into the substrate selection by the enzyme.

    • Yuka Yashiro
    • , Yuriko Sakaguchi
    •  & Kozo Tomita

  • Article
    | Open Access

    Targeting the interaction between transcription factor TEAD and its co-repressor VGL4 is an attractive strategy to chemically modulate Hippo signaling. Here, the authors develop a proteomimetic with stabilized tertiary structure that inhibits the TEAD:VGL4 interaction in vitro and in cells.

    • Hélène Adihou
    • , Ranganath Gopalakrishnan
    •  & Herbert Waldmann

  • Article
    | Open Access

    Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme and catalyzes 5α-reduction of testosterone to dihydrotestosterone. Structural analysis accompanied by computational and mutagenesis studies reveal the mechanisms of catalysis and inhibition by clinically relevant drugs targeting SRD5A2.

    • Qingpin Xiao
    • , Lei Wang
    •  & Cheng Zhang

  • Article
    | Open Access

    To overcome the limitation of FRET data being too sparse to cover all structural details, FRET experiments need to be carefully designed and complemented with simulations. Here the authors present a toolkit for automated design of FRET experiments, which determines how many and which FRET pairs should be used to maximize the accuracy, and for FRET-assisted structural modeling and refinement at the atomistic level.

    • Mykola Dimura
    • , Thomas-Otavio Peulen
    •  & Holger Gohlke

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