Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    Depletion of propellant in chemical-fuel-driven nanomotors is a limiting factor in device design and application. Here, the authors create a nitric-oxide-generating nanoparticle and explore cellular uptake and application of the nanomotors in nitric oxide treatments.

    • Mimi Wan
    • , Huan Chen
    •  & Jian Shen

  • Article
    | Open Access

    The Pseudomonas putida toxin GraT and antitoxin GraA form a type II toxin-antoxin module. Here the authors present the crystal structures of the GraA dimer, GraTA and GraA-DNA complexes and show that GraT contains a functionally important N-terminal intrinsic disordered region that prevents the binding of the GraTA complex to the operator.

    • Ariel Talavera
    • , Hedvig Tamman
    •  & Remy Loris

  • Article
    | Open Access

    Autophagic cells coordinate substrate remodeling with sequestration during autophagosome formation. Here, the authors show that during Parkin-mediated mitophagy, mitochondria are disassembled into progressively smaller aggregates near autophagy initiation sites in a PtdIns(4,5)P2-dependent manner.

    • Cheng-Wei Hsieh
    •  & Wei Yuan Yang

  • Article
    | Open Access

    A number of disease-causing human transthyretin (TTR) mutations are known to lead to amyloid formation. Here the authors combine neutron crystallography, native mass spectrometry and modelling studies to characterize the T119M and S52P-TTR mutants, providing mechanistic insights into TTR amyloidosis.

    • Ai Woon Yee
    • , Matteo Aldeghi
    •  & V. Trevor Forsyth

  • Article
    | Open Access

    How dietary β-mannans are utilized by gut Gram-positive bacteria is unclear. Here, the authors uncover the enzymatic pathway for β-mannan metabolism in Roseburia intestinalis and show that these polysaccharides promote beneficial gut bacteria, highlighting a potential for β-mannan-based therapeutic interventions.

    • Sabina Leanti La Rosa
    • , Maria Louise Leth
    •  & Bjørge Westereng

  • Article
    | Open Access

    Bioconjugation is a promising process to manufacture conjugate vaccines, but currently employed enzymes cannot generate the full spectrum of bacterial glycoproteins. Here, the authors use an O-linking oligosaccharyltransferase to generate a polyvalent pneumococcal bioconjugate vaccine with polysaccharides containing glucose at their reducing end.

    • Christian M. Harding
    • , Mohamed A. Nasr
    •  & Mario F. Feldman

  • Article
    | Open Access

    Orthobunyaviruses (OBVs) cause severe disease in humans and farm animals, but the molecular basis for infection is not fully understood. Here, the authors present crystal structures of free and antibody-bound OBV envelope glycoproteins and show that their domains enable efficient immunization in a mouse model.

    • Jan Hellert
    • , Andrea Aebischer
    •  & Félix A. Rey

  • Article
    | Open Access

    The enzyme serine hydroxymethyltransferase (SHMT) has been implicated in several diseases, however is hard to investigate. Here, the authors used a design strategy based on the retro-aldol-type reaction catalyzed by SHMT to develop SHMT-responsive fluorescence and 19F NMR molecular probes.

    • Hiroshi Nonaka
    • , Yuki Nakanishi
    •  & Shinsuke Sando

  • Article
    | Open Access

    The main components of tight junctions (TJ) are claudins that polymerize and form meshwork architectures called TJ strands. Here the authors present the 3.6 Å crystal structure of murine claudin-3 and show that residue P134 causes a bending of the third transmembrane helix which affects the morphology and adhesiveness of the TJ strands.

    • Shun Nakamura
    • , Katsumasa Irie
    •  & Yoshinori Fujiyoshi

  • Article
    | Open Access

    Allosteric interactions are an important contributor to the catalytic properties of enzyme. Here the authors demonstrate—using the prototypical protein kinase PKA—that the allosteric cooperativity underscoring substrate recognition and product release are directly linked to changes in conformational entropy.

    • Yingjie Wang
    • , Manu V.S.
    •  & Gianluigi Veglia

  • Article
    | Open Access

    Serine/threonine phosphatases such as PP1 associate with a large array of subunit proteins, such as ASPP (apoptosis-stimulating protein of p53) to achieve selective targeting. Here authors solved the crystal structure of the human ASPP2/PP1 complex and explain how ASPP2 can distinguish between PP1 isoforms.

    • M. Teresa Bertran
    • , Stéphane Mouilleron
    •  & Nicolas Tapon

  • Article
    | Open Access

    Large-scale deletions of mitochondrial DNA (mtDNA) are associated with different human mitochondrial diseases and normal human ageing. Here the authors present a model for mtDNA formation based on generation sequencing analysis of patients samples and in vitro reconstituted mtDNA deletion using purified proteins.

    • Örjan Persson
    • , Yazh Muthukumar
    •  & Maria Falkenberg

  • Article
    | Open Access

    SecB homologs can be associated with stress-responsive type II toxin–antitoxin (TA) systems and form tripartite toxin-antitoxin-chaperone systems (TAC). Here the authors provide structural insights into TACs by presenting the crystal structure of the M. tuberculosis TA-associated SecB chaperone in complex with the C-terminal ChAD (chaperone addiction) extension of the antitoxin HigA1.

    • Valérie Guillet
    • , Patricia Bordes
    •  & Lionel Mourey

  • Article
    | Open Access

    No structural data have been available for RNA polymerase holoenzymes or transcription initiation complexes that contain extracytoplasmic σ factors. Here the authors report the crystal structures of transcription initiation complexes comprising Mycobacterium tuberculosis RNA polymerase, extracytoplasmic σ factor σL and promoter DNA.

    • Wei Lin
    • , Sukhendu Mandal
    •  & Richard H. Ebright

  • Article
    | Open Access

    The antitermination factor RfaH adopts two functional states where its C-terminal domain is folded either as an α-helical hairpin or β-barrel. Here the authors employ solution state NMR measurements to show that the C-terminal domain transforms into the β-barrel only upon binding to the elongation complex and refolds back after dissociation.

    • Philipp Konrad Zuber
    • , Kristian Schweimer
    •  & Stefan H. Knauer

  • Article
    | Open Access

    How the chromosome passenger complex (CPC) phosphorylates the kinetochores that can be a micron away to control mitotic events is unknown. Here the authors find that the CPC directly binds microtubules near inner centromeres, which controls its ability to phosphorylate kinetochores independently of tension generated by kinetochore microtubule attachments.

    • Prasad Trivedi
    • , Anatoly V. Zaytsev
    •  & P. Todd Stukenberg

  • Article
    | Open Access

    Class F receptors are therapeutic targets in human disease and understanding their structural changes during receptor activation may provide important pharmacological insight. Here, the authors combine computational and experimental methods to identify a molecular switch in TM6/7 of Class F receptors that mediates receptor activation.

    • Shane C. Wright
    • , Paweł Kozielewicz
    •  & Gunnar Schulte

  • Article
    | Open Access

    Cryo-electron microscopy can determine the structure but not the nanomechanics of biological matter. Here the authors combine force spectroscopy in cryogenic conditions with computer simulations to characterize the properties of DNA simultaneously down to the sub-nm level.

    • Rémy Pawlak
    • , J. G. Vilhena
    •  & Ernst Meyer

  • Article
    | Open Access

    Many 2-Cystein Peroxiredoxins (Prx) can either function as peroxidases or chaperones when exposed to stress. Here the authors present the structures of Leishmania infantum mitochondrial Prx alone and with a bound model client protein, use crosslinking to reveal interaction regions that stabilize the bound client, and provide insights into the mechanism by which Prx’s adopt chaperone activity.

    • Filipa Teixeira
    • , Eric Tse
    •  & Ursula Jakob

  • Article
    | Open Access

    Elp3 is the catalytic subunit of the eukaryotic Elongator complex that catalyzes posttranscriptional tRNA modifications. Here the authors present the crystal structures of an acetyl-CoA analog bound bacterial Elp3 and a monomeric archaeal Elp3 and show that Elp3 functions as a tRNA modification enzyme in all domains of life.

    • Ting-Yu Lin
    • , Nour El Hana Abbassi
    •  & Sebastian Glatt

  • Article
    | Open Access

    Insulin-related gene (Insig) negatively regulates hepatic fatty acid synthesis, a process involved in development of non-alcoholic fatty liver disease (NAFLD). Here, the authors show that AMPK activation by metformin promotes Insig phosphorylation, stabilizing it and inhibiting lipogenic gene expression. This is protective against steatosis in diabetic mice.

    • Yamei Han
    • , Zhimin Hu
    •  & Yu Li

  • Article
    | Open Access

    Zinc ions (Zn2+) are imported by Golgi-resident transporters but the function of zinc in the early secretory pathway has remained unknown. Here the authors find that Zn2+ regulates protein quality control in the early secretory pathway by demonstrating that the pH-sensitive chaperone ERp44 binds Zn2+ and solving the Zn2+-bound ERp44 structure.

    • Satoshi Watanabe
    • , Yuta Amagai
    •  & Kenji Inaba

  • Article
    | Open Access

    Antibodies against Plasmodium falciparum merozoites that fix complement can inhibit blood-stage replication. Here, Reiling et al. show that complement-fixing antibodies strongly correlate with protective immunity in children, identify the merozoite targets, and predict antigen combinations that should result in strong protection.

    • Linda Reiling
    • , Michelle J. Boyle
    •  & James G. Beeson

  • Article
    | Open Access

    The TERB1-TERB2-MAJIN complex mediates the attachment of telomeres to the nuclear envelope. Here the authors present the crystal structures of the human TERB1-TERB2 and TERB2-MAJIN subcomplexes and show that Terb2 mutations, which abolish complex formation cause aberrant homologous pairing and disordered synapsis in mouse.

    • Yan Wang
    • , Yanyan Chen
    •  & Ming Lei

  • Article
    | Open Access

    The role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in maintenance of protein folding homeostasis inside the ER has remained unclear. Here the authors determine the structure of the complex between MANF and the ER-localized chaperone BiP and provide evidence that MANF serves as an anti-nucleotide exchange factor for BiP.

    • Yahui Yan
    • , Claudia Rato
    •  & David Ron

  • Article
    | Open Access

    Mother Nature is a valuable resource for the discovery of drug and agricultural chemicals. Here, the authors show that 7-deoxy-sedoheptulose produced by a cyanobacterium is an antimicrobial and herbicidal compound that acts through inhibition of 3-dehydroquniate synthase in the shikimate pathway.

    • Klaus Brilisauer
    • , Johanna Rapp
    •  & Karl Forchhammer

  • Article
    | Open Access

    PGAM5 is a mitochondrial protein phosphatase whose functions include regulation of mitophagy and cell death. Here, the authors use x-ray crystallography and EM to show that PGAM5 forms dodecameric rings and filaments in solution, and find that PGAM5 rings are essential for catalysis and for a structural effect PGAM5 has on mitochondrial membranes, independently of catalytic activity.

    • Karen Ruiz
    • , Tarjani M. Thaker
    •  & Natalia Jura

  • Article
    | Open Access

    Rix7 is a type II AAA-ATPase that is required for the assembly of the large ribosomal subunit. Here the authors present the 4.5 Å cryo-EM structure of the Rix7 homohexamer with a polypeptide fragment bound in its central channel and provide insights into the function of Rix7 as a molecular unfoldase.

    • Yu-Hua Lo
    • , Mack Sobhany
    •  & Robin E. Stanley

  • Article
    | Open Access

    Membraneless compartments have been theorized to be prebiotic micro-compartments as they spontaneously encapsulate RNA and proteins. Here, the authors report membraneless compartments can enhance RNA chemistries, affecting template directed RNA polymerization and stimulating nucleic acid enzymes.

    • Raghav R. Poudyal
    • , Rebecca M. Guth-Metzler
    •  & Philip C. Bevilacqua

  • Article
    | Open Access

    Designing interfaces that can induce protein-protein interactions is a challenging problem. Here the authors show that a five amino acid sequence known to mediate domain swapping in cystatins can drive oligomerization when grafted onto functionally and structurally unrelated host proteins, providing a simple approach to the design of protein assemblies.

    • Neha Nandwani
    • , Parag Surana
    •  & Shachi Gosavi

  • Article
    | Open Access

    The chaperone Hsp90 is a potential target for the development of drugs against fungal pathogens. Here the authors determine the structure of the Hsp90 nucleotide-binding domain from Candida albicans, which they use to design an inhibitor and demonstrate its selectivity for the fungal enzyme, both biochemically and in cells.

    • Luke Whitesell
    • , Nicole Robbins
    •  & Leah E. Cowen

  • Article
    | Open Access

    Hippo signaling leads to the phosphorylation of the key transcriptional effector, Yap/Yki, although how Yap/Yki stability is regulated has remained unclear. Here, Sun et al. identify HAUSP/Usp7 as a conserved and clinically relevant regulator of the Hippo pathway that increases Yap/Yki stability.

    • Xiaohan Sun
    • , Yan Ding
    •  & Zizhang Zhou

  • Article
    | Open Access

    Plants are dependent on controlled sugar uptake via Monosaccharide Transporters, such as STP10, for correct organ development, sugar accumulation in fruits and microbial defense. Here authors present the crystal structure of STP10 bound to glucose which sheds light on the fundamental principles of sugar transport in the plant-unique MST superfamily.

    • Peter Aasted Paulsen
    • , Tânia F. Custódio
    •  & Bjørn Panyella Pedersen

  • Article
    | Open Access

    Little is known about the degradation pathway of cyclic imines that are frequently found in bioactive secondary metabolites. Here, the authors found and characterised a copper amine oxidase, HarA that catalyses a ring-opening reaction of cyclic imine in harmaline and oxidative deamination of amines.

    • Toshiki Nagakubo
    • , Takuto Kumano
    •  & Michihiko Kobayashi

  • Article
    | Open Access

    Somatic alterations in the exonuclease domain of DNA polymerase ɛ have been linked to the development of highly mutated cancers. Here, the authors report that a major consequence of the most common cancer-associated Polɛ variant is a dramatically increased DNA polymerase activity.

    • Xuanxuan Xing
    • , Daniel P. Kane
    •  & Polina V. Shcherbakova

  • Article
    | Open Access

    Enhanced Wnt receptor activity is a major cause of cancer development. Here the authors identify camelid single-domain antibody fragments (VHHs) that bind to the Wnt receptor LRP5/6 ectodomain, determine the crystal structures and show that these VHHs selectively inhibit Wnt3- mediated cellular responses and block the growth of mutant Wnt-hypersensitive intestinal tumor organoids.

    • Nicola Fenderico
    • , Revina C. van Scherpenzeel
    •  & Madelon M. Maurice

  • Article
    | Open Access

    The interactions of lignin with polysaccharides in plant secondary cell walls are not well understood. Here the authors employ solid-state NMR measurements to analyse intact stems of maize, Arabidopsis, switchgrass and rice and observe that lignin self-aggregates and forms highly hydrophobic microdomains that make extensive surface contacts to xylan.

    • Xue Kang
    • , Alex Kirui
    •  & Tuo Wang

  • Article
    | Open Access

    Host metabolic reprogramming plays a role in functional responses against pathogens. Here, the authors characterise malonylated proteins in macrophages and show that malonylation of the glycolytic enzyme GAPDH impacts cytokine production by modulating both its enzymatic activity and RNA-binding capacity.

    • Silvia Galván-Peña
    • , Richard G. Carroll
    •  & Luke A. O’Neill

  • Article
    | Open Access

    Beta II protein kinase C (βIIPKC) activation contributes to heart failure. Here the authors show, in a rat model of myocardial infarction, that heart failure outcome can be improved by selectively inhibiting the interaction between βIIPKC and its downstream mitochondrial target Mitofusin-1, and that this strategy is superior to global βIIPKC inhibition.

    • Julio C. B. Ferreira
    • , Juliane C. Campos
    •  & Daria Mochly-Rosen

  • Article
    | Open Access

    Spatial proteomics allows studying cellular protein localisations at system-wide scale. Here, the authors show that combining the previously developed hyperLOPIT method with differential centrifugation yields protein localisation maps at suborganellar resolution while reducing analysis time and input material.

    • Aikaterini Geladaki
    • , Nina Kočevar Britovšek
    •  & Kathryn S. Lilley

  • Article
    | Open Access

    Glucocorticoids (GCs) are widely used anti-inflammatory drugs; however, long-term treatment causes metabolic side effects. Here, the authors show that E47 is a modulator of glucocorticoid receptor activity for a subset of target genes in mouse liver, and that loss of E47 protects mice from hyperglycemia and hepatic steatosis in response to GCs.

    • M. Charlotte Hemmer
    • , Michael Wierer
    •  & N. Henriette Uhlenhaut

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