Structural biology articles within Nature Communications

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  • Article
    | Open Access

    SxtT and GxtA are Rieske oxygenases that are involved in paralytic shellfish toxin biosynthesis and catalyze monohydroxylation reactions at different positions on the toxin scaffold. Here, the authors present crystal structures of SxtT and GxtA with the native substrates β-saxitoxinol and saxitoxin as well as a Xenon-pressurized structure of GxtA, which reveal a substrate access tunnel to the active site. Through structure-based mutagenesis studies the authors identify six residues in three different protein regions that determine the substrate specificity and site selectivity of SxtT and GxtA. These findings will aid the rational engineering of other Rieske oxygenases.

    • Jianxin Liu
    • , Jiayi Tian
    •  & Jennifer Bridwell-Rabb

  • Article
    | Open Access

    Topoisomerase I (TOP1) relaxes both positive and negative supercoils by nicking DNA and after rotation of the broken DNA strand closes the nick. Here, the authors present the DNA free crystal structure of TOP1 from the hyperthermophilic archaeon Caldiarchaeum subterraneum in the open form and discuss the mechanism of how DNA enters the catalytic site of TOP1.

    • Diane T. Takahashi
    • , Danièle Gadelle
    •  & Claudine Mayer

  • Article
    | Open Access

    The bacterial Cyclic-oligonucleotide-Based Anti-phage Signaling System (CBASS) contains a CD-NTase that synthesizes cyclic di- and tri-nucleotides, and bacterial STING proteins recognize c-di-GMP generated by CD-NTase during phage infection and signal the infected bacteria to commit suicide. Here, the authors provide insights into the molecular basis for c-di-GMP recognition of bacterial STING proteins by determining two STING protein crystal structures with bound c-di-GMP from Prevotella corporis and Myroides sp. ZB35.

    • Tzu-Ping Ko
    • , Yu-Chuan Wang
    •  & Yeh Chen

  • Article
    | Open Access

    The iodinated thyroglobulin functions as iodine storage and carrier protein and a precursor for thyroid hormone (TH) biogenesis. Here, the authors report the structure of native, fully glycosylated human thyroglobulin, revealing the location of the hTg hormonogenic and glycosylation sites.

    • Ricardo Adaixo
    • , Eva M. Steiner
    •  & Nicholas M. I. Taylor

  • Article
    | Open Access

    Triclosan (TCS), an antimicrobial agent commonly found in consumer products, has been reported to exacerbates colitis in animal models. Here, using in vitro and in vivo approaches, the authors show that gut bacterial enzymes can drive the metabolic activation and gut toxicity of TCS, highlighting an important role of intestinal microbial factors in the complex etiology of colitis.

    • Jianan Zhang
    • , Morgan E. Walker
    •  & Guodong Zhang

  • Article
    | Open Access

    The glucagon-like peptide-1 receptor (GLP-1R) can be targeted in the treatment of diabetes, obesity and other metabolic disorders. Here, the authors assess the molecular mechanisms of peptide agonists binding to GLP-1R and the responses elucidated by these ligands, including distinct kinetics of G protein activation.

    • Giuseppe Deganutti
    • , Yi-Lynn Liang
    •  & Denise Wootten

  • Article
    | Open Access

    AlphaFold2 has originally been developed to provide highly accurate predictions of protein monomer structures. Here, the authors present a simple adaptation of AlphaFold2 that enables structural modeling of peptide–protein complexes, and explore the underlying mechanisms and limitations of this approach.

    • Tomer Tsaban
    • , Julia K. Varga
    •  & Ora Schueler-Furman

  • Article
    | Open Access

    There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model.

    • Alexander I. Kostyuk
    • , Maria-Armineh Tossounian
    •  & Vsevolod V. Belousov

  • Article
    | Open Access

    TCPTP is a non-receptor type protein tyrosine phosphatase involved in various signalling pathways. Here, the authors provide structural insights into TCPTP activation, showing that TCPTP is inhibited by its C-terminal tail, which can be displaced by the cytosolic tail of integrin-α1, leading to activation.

    • Jai Prakash Singh
    • , Yang Li
    •  & Tzu-Ching Meng

  • Article
    | Open Access

    Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of the catecholamine neurotransmitters and hormones dopamine (DA), adrenaline and noradrenaline. Here, the authors present the cryo-EM structures of full-length human TH in the apo form and bound with DA, as well as the structure of Ser40 phosphorylated TH, and discuss the inhibitory and stabilizing effects of DA on TH and its counteraction by Ser40-phosphorylation.

    • María Teresa Bueno-Carrasco
    • , Jorge Cuéllar
    •  & José M. Valpuesta

  • Article
    | Open Access

    Structural immunology is critical in understanding the interplay between the immune response and the infective agent but such studies in T cells and SARS-CoV-2 lag behind those of antibodies and B-cell receptors. Here the authors assess recognition of SARS-CoV-2 spike epitopes and their natural variants by public and private T cell receptors.

    • Daichao Wu
    • , Alexander Kolesnikov
    •  & Roy A. Mariuzza

  • Article
    | Open Access

    Here, the authors present the cryo-EM structure of in vitro amyloid fibrils from recombinant SAA1.1 protein that were formed by seeding with fibrils purified from systemic AA amyloidosis tissue. This in vitro fibril structure resembles the structure of the ex vivo fibrils but differs from unseeded in vitro fibrils. These findings show that fibril morphologies can be propagated in vitro by seeding.

    • Thomas Heerde
    • , Matthies Rennegarbe
    •  & Marcus Fändrich

  • Article
    | Open Access

    The authors present a strategy to construct dynamic biomolecular landscapes. Here, they derive a quantitative description of the distribution timescales and amplitudes of reorientational motion of POPC membranes from the combination of NMR relaxation data and frame analysis of MD simulations.

    • Albert A. Smith
    • , Alexander Vogel
    •  & Daniel Huster

  • Article
    | Open Access

    Here, the authors provide insights into the conformational dynamics of the Beta and Kappa SARS-CoV-2 spike (S) proteins by determining their cryo-EM structures, which revealed a distribution shift towards the open state for both variants compared to the wild-type S protein. They also present the structures of the Kappa and Beta S-ACE2 complexes, where a population shift towards the three receptor-binding domain up conformation was observed. In combination with biochemical data these structures show how the S protein variants efficiently recognize and bind to ACE2.

    • Yifan Wang
    • , Cong Xu
    •  & Yao Cong

  • Article
    | Open Access

    Rpn13 is a substrate receptor of the 26S proteasome and an anti-cancer drug target. Here, the authors identify and characterize XL5, a lead compound that binds to the N-terminal Pru domain of human Rpn13 (hRpn13), solve the NMR structure of XL5-ligated hRpn13 Pru and develop XL5-PROTACs that preferentially target an identified hRpn13 Pru fragment present in multiple myeloma cells.

    • Xiuxiu Lu
    • , Venkata R. Sabbasani
    •  & Kylie J. Walters

  • Article
    | Open Access

    The intrinsic flexibility of membranes proteins still poses a challenge in determining their active structure. Here the authors describe the development of a method that combines chemical footprinting and mass spectrometry to assist in determining the structure of native membrane proteins and their dynamics.

    • Jie Sun
    • , Xiaoran Roger Liu
    •  & Michael L. Gross

  • Article
    | Open Access

    EF-G drives ribosomal translocation along mRNA. Time-resolved cryo-EM captured translocation with EF-G•GTP—without inhibitors—revealing how EF-G uses ribosome fluctuations to drive translocation and GTP hydrolysis to leave at the right moment.

    • Christine E. Carbone
    • , Anna B. Loveland
    •  & Andrei A. Korostelev

  • Article
    | Open Access

    Mitoribosomes are remarkably diverse in their structures and compositions. Here the authors combine biochemistry, genetics, single particle cryo-electron microscopy and in situ cryo-electron tomography to reveal the mitochondrial ribosome of Chlamydomonas reinhardtii as an extreme example of evolution and species-specific adaptation.

    • Florent Waltz
    • , Thalia Salinas-Giegé
    •  & Yaser Hashem

  • Article
    | Open Access

    Many RNA viruses employ programmed –1 ribosomal frameshifting (PRF) to expand their coding capacity and optimize production of viral proteins. Here, the authors report structural and biophysical analysis of protein 2A from a cardiovirus, with insights into the mechanism of its PRF-stimulatory function.

    • Chris H. Hill
    • , Lukas Pekarek
    •  & Ian Brierley

  • Article
    | Open Access

    Hedgehog-Interacting Protein (HHIP) is the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling. Here, the authors report structures of the HHIP N- and C-terminal domains, both in complexes with glycosaminoglycans, providing insights into the molecular basis for SHH sequestration and inhibition.

    • Samuel C. Griffiths
    • , Rebekka A. Schwab
    •  & Christian Siebold

  • Article
    | Open Access

    β-arrestins commonly bind to two distinct elements in GPCRs: the phosphorylated carboxyl terminal tail (C tail) and the cytoplasmic face of the transmembrane region (TM core). Here, the authors use methyl-TROSY NMR measurements to characterise the interactions between β-arrestin 1 (βarr1) and a GPCR and observe that C tail-mediated interaction with a GPCR alone induces the partial activation of βarr1, whereas the TM core- and C tail-mediated interactions together stabilize the activated conformation of βarr1.

    • Yutaro Shiraishi
    • , Yutaka Kofuku
    •  & Ichio Shimada

  • Article
    | Open Access

    Slowpoke (Slo) channels are voltage-gated potassium channels that are activated by high intracellular Ca2+ concentrations, and they are targets for insecticides and antiparasitic drugs. Here, the authors present the cryo-EM structures of the Drosophila melanogaster Slo channel in the Ca2+-bound and Ca2+-free conformations, as well as in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside and discuss the mechanisms by which they affect the activity of Slo.

    • Tobias Raisch
    • , Andreas Brockmann
    •  & Stefan Raunser

  • Article
    | Open Access

    Systemic ATTR amyloidosis causes the abnormal accumulation of ATTR fibrils formed from the human plasma protein transthyretin (TTR) in multiple organs including the eye. Here, the authors present a 3.2 Å cryo-EM structure of an ATTR fibril isolated from the vitreous body of an ATTR patient’s eye and discuss the mechanism for the structural conversion of TTR into a fibrillar form.

    • Irina Iakovleva
    • , Michael Hall
    •  & A. Elisabeth Sauer-Eriksson

  • Article
    | Open Access

    The β-barrel assembly machinery (BAM) assists the folding and membrane insertion of bacterial outer membrane proteins. Here, the authors report structural characterization of BAM in lipid environment and in complex with the client protein EspP integrated into the barrel of BamA, providing insight into BAM mechanism of function.

    • Runrun Wu
    • , Jeremy W. Bakelar
    •  & Nicholas Noinaj

  • Article
    | Open Access

    System xc- is a cystine transporter that is expressed in the plasma membrane and imports cystine in exchange for intracellular glutamate. Here, the authors present the cryo-EM structure of human system xc- both in the apo form and the glutamate bound state, and further supported by molecular dynamics and cell-based assays they discuss its cystine transport mechanism.

    • Joanne L. Parker
    • , Justin C. Deme
    •  & Simon Newstead

  • Article
    | Open Access

    Here the authors show that a viral protein interferes with the binding of phosphorylated eIF2 to eIF2B, thereby suppressing the host integrated stress response (ISR). This suppression of the ISR abrogates translational changes of the host and ameliorates neurite degradation under stress.

    • Kazuhiro Kashiwagi
    • , Yuichi Shichino
    •  & Takuhiro Ito

  • Article
    | Open Access

    The tumor suppressor p53 is mutated in more than half of human cancers and the compound methylene quinuclidinone (MQ) was shown to reactivate p53 mutants by binding covalently to cysteine residues. Here, the authors present crystal structures of wild-type and cancer related p53 mutant core domains bound to MQ alone and in complex with their DNA response elements and observe that MQ is bound to several cysteine residues located at the surface of the core domain.

    • Oksana Degtjarik
    • , Dmitrij Golovenko
    •  & Zippora Shakked

  • Article
    | Open Access

    The authors present DeepRank, a deep learning framework for the data mining of large sets of 3D protein-protein interfaces (PPI). They use DeepRank to address two challenges in structural biology: distinguishing biological versus crystallographic PPIs in crystal structures, and secondly the ranking of docking models.

    • Nicolas Renaud
    • , Cunliang Geng
    •  & Li C. Xue

  • Article
    | Open Access

    SPX proteins sense phosphate levels in plant cells by binding to inositol polyphosphates (InsP) and suppressing the activity of PHR transcription factors. Here the authors show that when bound to InsP6, the rice SPX1 protein inhibits the activity of PHR2 by attenuating both its dimerization and DNA binding activity.

    • Jia Zhou
    • , Qinli Hu
    •  & Weiman Xing

  • Article
    | Open Access

    Eph receptor tyrosine kinases and their ephrin ligands mediate cell-cell communication. Here, the authors assess the structure and dynamics of the EphA2 intracellular region and uncover complex effects of phosphorylation within the linker region between EphA2 kinase and SAM domains.

    • Bernhard C. Lechtenberg
    • , Marina P. Gehring
    •  & Elena B. Pasquale

  • Article
    | Open Access

    Steviol glycosides from the plant Stevia rebaudiana are already used as lowcalorie sweeteners, but the most abundant naturally occurring compounds have a bitter aftertaste. Here, the authors characterize and engineer rice glycosyltransferase OsUGT91C1 to facilitate the large-scale production of naturally rare but palatable glycosides Reb D and Reb M

    • Jinzhu Zhang
    • , Minghai Tang
    •  & Wei Cheng

  • Article
    | Open Access

    UvrD is a model helicase from the non-hexameric Superfamily 1. Here, the authors use optical tweezers to measure directly the stepwise translocation of UvrD along a DNA hairpin, and propose a mechanism in which UvrD moves one base pair at a time, but sequesters the nascent single strands, releasing them after a variable number of ATP hydrolysis cycles.

    • Sean P. Carney
    • , Wen Ma
    •  & Yann R. Chemla

  • Article
    | Open Access

    Rearrangement hot spots (Rhs) proteins are bacterial polymorphic toxin systems. Here, the authors show that Rhs1 forms a complex with the Type VI secretion system (T6SS) spike protein VgrG and the EagR chaperone. They also present the cryo-EM structure of the Rhs1-EagR complex and propose a model for Rhs loading and delivery by the T6SS.

    • Dukas Jurėnas
    • , Leonardo Talachia Rosa
    •  & Eric Cascales

  • Article
    | Open Access

    CDP-diacylglycerol (CDP-DAG) alcohol O-phosphatidyl transferases (CDP-APs) are conserved in archaea, bacteria, and eukaryotes and catalyze the de novo synthesis of phospho-lipids from the precursor CDP-DAG and an alcohol. Here, the authors present the crystal structures of the Methanocaldococcus jannaschii phosphatidyl serine synthase (MjPSS) in four different states and suggest a model for its catalytic mechanism.

    • Martin Centola
    • , Katharina van Pee
    •  & Özkan Yildiz

  • Article
    | Open Access

    Ty3 retrotransposon integrates with an exquisite specificity upstream of RNA Polymerase III-transcribed genes, such as transfer RNAs. Here the authors resolve a cryo-EM structure of an active Ty3 intasome in complex with a TFIIIB-bound tRNA promoter, shedding light into the molecular determinants of harmless retrotransposition.

    • Guillermo Abascal-Palacios
    • , Laura Jochem
    •  & Alessandro Vannini

  • Article
    | Open Access

    The venom of Latrodectus spiders contains seven Latrotoxins (LaTXs), among them α-latrocrustatoxin (LCT) and δ- latroinsectotoxins δ-LIT. LaTXs bind to specific receptors on the surface of neuronal cells and target the molecular exocytosis machinery. Here, the authors present the cryo-EM structure of the α-LCT monomer and the δ-LIT dimer, which reveal that LaTXs are organized in four domains and they discuss the potential oligomerisation mechanism that takes place before LaTXs membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions.

    • Minghao Chen
    • , Daniel Blum
    •  & Christos Gatsogiannis

  • Article
    | Open Access

    Dispatched (Disp) RND transporter, activated by Furin-mediated proteolytic cleavage, mediates the release of the lipid-modified Hedgehog (Hh) ligands. Here, the authors report structures of human Disp1 (hDisp1) before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh), with insights into the mechanisms of hDisp1 activation and function.

    • Wanqiu Li
    • , Linlin Wang
    •  & Xin Gong

  • Article
    | Open Access

    Microbial DNA glycosylases associated with the biosynthesis of DNA-damaging antibiotics have evolved self-resistance for their cognate natural products. Here, the authors provide evidence that cellular self-resistance is enabled by reduced affinity of the glycosylases for the excision products of the corresponding DNA lesions.

    • Elwood A. Mullins
    • , Jonathan Dorival
    •  & Brandt F. Eichman

  • Article
    | Open Access

    Tweety Homologs (TTYHs) are highly conserved membrane proteins, whose functions remain poorly understood. Here, the authors present the cryo-EM structures of murine TTYH2 and TTYH3 that form cis-dimers in the presence of Ca2+, whereas in the absence of Ca2+ TTYH2 adopts monomeric and trans-dimeric structures. The presented structures lack ion conducting pathways, which is consistent with results from electrophysiology measurements.

    • Baobin Li
    • , Christopher M. Hoel
    •  & Stephen G. Brohawn

  • Article
    | Open Access

    Vpr is a HIV-1 accessory virulence factor that also interacts with the human DNA repair protein hHR23A. Here, the authors present the structure of Vpr in complex with the C-terminal half of hHR23A comprising the XPC-binding and ubiquitin-associated domains, which reveals that hHR23A interacts with the DCAF1-binding and not the substrate-binding Vpr surface and further illustrates how Vpr acts as a versatile structural adapter that targets diverse DNA repair pathways.

    • In-Ja L. Byeon
    • , Guillermo Calero
    •  & Angela M. Gronenborn

  • Article
    | Open Access

    Resistance-nodulation-cell division (RND)-type tripartite efflux pumps confer multidrug resistance to Gram-negative bacteria. Here, structural and functional analyses of AdeB from Acinetobacter baumannii and AcrB from Escherichia coli provide insight into their different drug-binding and conformational drug transport states.

    • Alina Ornik-Cha
    • , Julia Wilhelm
    •  & Klaas M. Pos

  • Article
    | Open Access

    The RNA genome of the Hepatitis C Virus binds to the liver-specific miR122. Here the authors report the crystal structure of the Ago2:miR122:HCV complex showing that the viral RNA’s structural element traps the Ago2:miR-122 complex on the 5’ end of the viral genome to protect it from degradation.

    • Luca F. R. Gebert
    • , Mansun Law
    •  & Ian J. MacRae

  • Article
    | Open Access

    Simultaneous targeting of BCL-xL and BCL-2 is an attractive approach for cancer treatment. Based on information gained by computational structure modelling, the authors develop a PROTAC that induces degradation of both BCL-xL and BCL-2 and effectively targets BCL-xL/2-dependent leukaemia cells.

    • Dongwen Lv
    • , Pratik Pal
    •  & Daohong Zhou

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