Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    The complement membrane attack complex (MAC) is a lytic immune pore that kills pathogens. Here the authors use cryoEM to provide a structural and biophysical mechanism for how β-pore forming proteins breach the lipid bilayer, providing pathways to explore pore-formation in molecular detail.

    • Anaïs Menny
    • , Marina Serna
    •  & Doryen Bubeck

  • Article
    | Open Access

    Tropinone is an intermediate in the biosynthesis of tropane alkaloids. Here, the authors discovered the enzymes AbPYKS and AbCYP82M3, a non-canonical polyketide synthase and a cytochrome P450, that work sequentially to form tropinone from N-methyl-Δ1-pyrrolinium cation.

    • Matthew A. Bedewitz
    • , A. Daniel Jones
    •  & Cornelius S. Barry

  • Article
    | Open Access

    The molecular basis of ultrahigh specificity in protein-protein interactions remains obscure. The authors present a computational method to design atomically accurate new pairs exhibiting >100,000-fold specificity switches, generating a large and complex interaction network.

    • Ravit Netzer
    • , Dina Listov
    •  & Sarel J. Fleishman

  • Article
    | Open Access

    The catalytic efficiency of many enzymes is lower than the theoretical maximum. Here, the authors combine genome-scale metabolic modeling with population genetics models to simulate enzyme evolution, and find that strong epistasis limits turnover numbers due to diminishing returns of fitness gains.

    • David Heckmann
    • , Daniel C. Zielinski
    •  & Bernhard O. Palsson

  • Article
    | Open Access

    Integral membrane proteins are assembled into the ER membrane via the ribosome-translocon channel. Here authors use in vitro translation assays and MD simulations to show that folding in the ribosome is favorable for TM helices, but unfavorable for soluble helices.

    • Manuel Bañó-Polo
    • , Carlos Baeza-Delgado
    •  & Ismael Mingarro

  • Article
    | Open Access

    Drp1 and Dnm2 have been implicated in mitochondrial fission events, although their specific activities in constriction and scission have been unclear. Here, the authors demonstrate that Drp1 is sufficient to constrict and sever mitochondrial and peroxisomal membranes in the absence of Dnm proteins.

    • Sukrut C. Kamerkar
    • , Felix Kraus
    •  & Michael T. Ryan

  • Article
    | Open Access

    Cubilin and the transmembrane protein amnionless (AMN) form the endocytic receptor cubam that is essential for intestinal vitamin B12 uptake. Here the authors present the 2.3 Å crystal structure of AMN in complex with the amino-terminal region of cubilin and discuss cubam architecture and disease causing mutations.

    • Casper Larsen
    • , Anders Etzerodt
    •  & Christian Brix Folsted Andersen

  • Article
    | Open Access

    Ubiquitin and ubiquitin-like modifiers such as SUMO play important roles in several cellular pathways that can become deregulated in cancer. Here the authors describe the structural basis for inhibition of SUMO E1 ligase by the small molecule COH000.

    • Zongyang Lv
    • , Lingmin Yuan
    •  & Shaun K. Olsen

  • Review Article
    | Open Access

    In this review, Aravin and colleagues examine bacterial and archaeal Argonaute proteins, discuss their diverse architectures and their possible roles in host defense, proposing additional functions for Argonaute proteins in prokaryotic cells.

    • Lidiya Lisitskaya
    • , Alexei A. Aravin
    •  & Andrey Kulbachinskiy

  • Article
    | Open Access

    Reduced insulin-like signaling is required for C. elegans response to many environmental stressors, but how distinct outcomes are achieved is unknown. The authors show that the cytosolic sulfotransferase SSU-1 controls neurohormonal signaling via NHR-1 to specify the animals’ osmotic stress response.

    • Nicholas O. Burton
    • , Vivek K. Dwivedi
    •  & H. Robert Horvitz

  • Article
    | Open Access

    Marine woodborers can digest woody biomass without the help of gut microbiota but the mechanism has remained unclear. Here, the authors provide evidence that the woodborer’s respiratory protein hemocyanin plays a central role in wood digestion and may offer a route toward biorefining of woody plant biomass.

    • Katrin Besser
    • , Graham P. Malyon
    •  & Simon J. McQueen-Mason

  • Article
    | Open Access

    The BAF complex is a multi-subunit chromatin remodeling complex that plays important roles in transcription regulation. Here the authors provide evidence that BRD9 and GLTSCR1/BICRA or its paralog GLTSCR1-like/BICRAL define a non-canonical BAF complex that regulates naive pluripotency in mouse embryonic stem cells.

    • Jovylyn Gatchalian
    • , Shivani Malik
    •  & Diana C. Hargreaves

  • Article
    | Open Access

    Data-independent acquisition (DIA)-based proteomics often relies on mass spectrum libraries from data-dependent acquisition experiments. Here, the authors present a method to generate DIA-based chromatogram libraries, enabling DIA-only workflows and detecting more peptides than with spectrum libraries alone.

    • Brian C. Searle
    • , Lindsay K. Pino
    •  & Michael J. MacCoss

  • Article
    | Open Access

    TUSC3 resides on chromosome 8p which is frequently deleted in advanced stage tumors. Here, the authors show that TUSC3 loss mediated by miR-224/-520c promotes NSCLC metastasis where it enhances ATF-6α-dependent UPR and HRD-1 dependent ERAD, which in turn suppress p53-NM23H1/2 tumor suppressor pathway.

    • Young-Jun Jeon
    • , Taewan Kim
    •  & Carlo M. Croce

  • Article
    | Open Access

    Endocannabinoid signaling regulates food intake and is a potential therapeutic target for obesity. Here the authors show that adipocyte O-GlcNAc transferase (OGT) is required for high fat diet-induced hyperphagia via transcriptional activation of de novo lipid desaturation and accumulation of an endogenous appetite-inducing cannabinoid.

    • Min-Dian Li
    • , Nicholas B. Vera
    •  & Xiaoyong Yang

  • Article
    | Open Access

    In plants, hyperosmolality stimuli triggers opening of the osmosensitive channels, leading to a rapid downstream signaling cascade. Here, the authors solve the cryo-EM structure of an osmosensitive channel from Arabidopsis OSCA1.2 in its inactivated state.

    • Xin Liu
    • , Jiawei Wang
    •  & Linfeng Sun

  • Article
    | Open Access

    Efficient biosynthesis of lactams is still undesirable due to lacking of suitable enzyme. Here, the authors develop a sensitive transcription factor-based biosensor for high-throughput screening of marine metagenome and find a cyclase that can cyclize ω-amino fatty acids to lactam.

    • Soo-Jin Yeom
    • , Moonjeong Kim
    •  & Seung-Goo Lee

  • Article
    | Open Access

    The microalgal pyrenoid has been reported to behave as a phase-separated liquid compartment. Here the authors demonstrate that the CO2-fixing enzyme Rubisco and the linker protein EPYC1 are necessary and sufficient to bring about a liquid-liquid phase separation that recapitulates the pyrenoid’s liquid-like behavior.

    • Tobias Wunder
    • , Steven Le Hung Cheng
    •  & Oliver Mueller-Cajar

  • Article
    | Open Access

    Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase, which requires the leading-strand polymerase Pol ɛ. Here the authors present a structural analysis of a CMG Pol ɛ on a DNA fork, providing insight on the steps leading productive helicase engagement to the DNA junction.

    • Panchali Goswami
    • , Ferdos Abid Ali
    •  & Alessandro Costa

  • Article
    | Open Access

    The nucleolus is a membrane-less organelle and both Nucleophosmin (NPM1) and Surfeit locus protein 6 (SURF6) are abundant proteins within the nucleolus. Here the authors employ biophysical methods to study the properties of NPM1-S6N droplets and provide insights into the role of SURF6 in maintaining and modulating the liquid-like structure of the nucleolus.

    • Mylene C. Ferrolino
    • , Diana M. Mitrea
    •  & Richard W. Kriwacki

  • Article
    | Open Access

    Lysine degradation and the role of the metabolites glutarate and L-2-hydroxyglutarate have remained elusive in many organisms including Escherichia coli. Here authors present a pathway for catabolism of lysine to succinate in E. coli involving glutarate and L-2-hydroxyglutarate as intermediates.

    • Sebastian Knorr
    • , Malte Sinn
    •  & Jörg S. Hartig

  • Article
    | Open Access

    Complex RNA three-dimensional structures undergo functionally important programmed conformational changes. Here, the authors report how two structurally and functionally coupled RNA domains within a viral 3′-UTR sense the ribosome through conformational changes and respond by modulating translation.

    • Erik W. Hartwick
    • , David A. Costantino
    •  & Jeffrey S. Kieft

  • Article
    | Open Access

    USP25 is a deubiquitinating enzyme and a positive regulator of Wnt/β-catenin signaling. Here the authors present the crystal structure of USP25 in a tetrameric inactive state and their biochemical and kinetic assays support an USP25 autoinhibitory mechanism that is mediated through a dimer to tetramerization transition.

    • Bing Liu
    • , Marta Sureda-Gómez
    •  & David Reverter

  • Article
    | Open Access

    The pathogen recognition receptors NOD1/2 recognize bacterial cell wall components and signal through their downstream adapter kinase RIP2 via a CARD (Caspase activation and recruitment domain) mediated oligomerization process. Here the authors present the cryo-EM structure of the active RIP2-CARD filament and discuss implications for NOD1/2-RIP2 signalling.

    • Qin Gong
    • , Ziqi Long
    •  & Bin Wu

  • Article
    | Open Access

    BAX and BAK are pro-apoptotic proteins whose activity is essential for the action of many anti-cancer drugs and to suppress tumorigenesis. Here, the authors perform a genome-wide CRISPR/Cas9 screen and identify VDAC2 as a promoter of BAX-mediated apoptosis that is important for an efficient chemotherapeutic response and to suppress tumor formation.

    • Hui San Chin
    • , Mark X. Li
    •  & Grant Dewson

  • Article
    | Open Access

    Myosin motors drive the actin cytoskeleton out-of-equilibrium, but the role of myosin-driven active stresses in the accumulation and dissipation of mechanical work is unclear. Here, the authors synthesize an actomyosin material and find that the rate of entropy production increases non-monotonically with increasing accumulation of active stresses.

    • Daniel S. Seara
    • , Vikrant Yadav
    •  & Michael P. Murrell

  • Article
    | Open Access

    Pancreatic ductal adenocarcinoma (PDAC) cells display varying degrees of reliance on oncogenic KRAS. Here the authors show that KRAS-resistant PDAC cells maintain nucleotides synthesis through a KRAS-independent upregulation of the non-oxidative pentose phosphate pathway gene RPIA and that targeting nucleotide metabolism restore sensitivity to KRAS pathway inhibition.

    • Naiara Santana-Codina
    • , Anjali A. Roeth
    •  & Alec C. Kimmelman

  • Article
    | Open Access

    The dynamics of protein acetylation during infection remains unexplored. Here, Murray et al. characterize spatio-temporal acetylations of both cellular and viral proteins during HCMV infection, providing new functional insights into the host-virus acetylome that might help identify new antiviral targets.

    • L. A. Murray
    • , X. Sheng
    •  & I. M. Cristea

  • Article
    | Open Access

    Topoisomerases solve topological problems during DNA metabolism, but their role in RNA metabolism remains unclear. Here the authors provide evidence that in Drosophila, Topoisomerase 3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) to promote heterochromatin formation and transcriptional silencing.

    • Seung Kyu Lee
    • , Yutong Xue
    •  & Weidong Wang

  • Article
    | Open Access

    Phytochromes are photoreceptors that are present in plants, bacteria and fungi. Here the authors present crystal structures of the phytochrome Agp2 from Agrobacterium fabrum in the parent Pfr state as well as a functional Meta-F intermediate and discuss mechanistic implications for photoconversion.

    • Andrea Schmidt
    • , Luisa Sauthof
    •  & Patrick Scheerer

  • Article
    | Open Access

    Mineralized plaque, or dental calculus, is a valuable reservoir of the ancient oral microbiome. Here, the authors use quantitative metaproteomics to analyze the dental calculus of 21 individuals from a medieval cemetery, identifying human and microbial proteins that shed light on their oral health status.

    • Rosa R. Jersie-Christensen
    • , Liam T. Lanigan
    •  & Jesper V. Olsen

  • Article
    | Open Access

    Soluble fumarate reductases are essential for eukaryotic cell survival under anaerobic conditions but their mechanism is not fully understood. Here, the authors present structural and enzymatic analyses of yeast fumarate reductase Osm1, elucidating the molecular basis of maintaining redox balance during anaerobiosis.

    • Sunghwan Kim
    • , Chang Min Kim
    •  & Hyun Ho Park

  • Article
    | Open Access

    The recognition of the mRNA codon by the tRNA anticodon is crucial for protein synthesis. Here the authors introduce non-standard nucleotides in bacterial and eukaryotic mRNA to reveal the minimal hydrogen bond requirement of codon-anticodon interaction for efficient and accurate translation.

    • Thomas Philipp Hoernes
    • , Klaus Faserl
    •  & Matthias David Erlacher

  • Article
    | Open Access

    The construction of complex RNA-delivered genetic circuits in mammalian cells is challenging, though offers advantages over DNA circuits in clinical use. Here the authors construct a set of logic gates that respond to multiple miRNAs and demonstrate an apoptosis-regulatory AND gate.

    • Satoshi Matsuura
    • , Hiroki Ono
    •  & Hirohide Saito

  • Article
    | Open Access

    Bacterial histidine kinases (HKs) play key roles in the response to stimuli and are regulated by reversible phosphorylation. Here, the authors show that the activity of a HK in the plant pathogen Xanthomonas campestris is modulated by irreversible, proteolytic modification in response to osmostress.

    • Chao-Ying Deng
    • , Huan Zhang
    •  & Wei Qian

  • Article
    | Open Access

    Transient receptor potential vanilloid channel 3 (TRPV3) responds to temperature and sensitizes upon repeated stimulation with either heat or agonists. Here authors present the cryo-EM structures of apo and sensitized human TRPV3 and describe the structural basis of sensitization.

    • Lejla Zubcevic
    • , Mark A. Herzik Jr.
    •  & Seok-Yong Lee

  • Article
    | Open Access

    Ubiquitination and ubiquitin-like modifications of proteins regulate multiple cellular processes but identifying substrates of specific E2 and E3 enzymes remains challenging. Here, the authors conjugate E2 enzymes with enrichable ubiquitin derivatives to identify substrates of specific E2/E3 pairs by mass spectrometry.

    • Gábor Bakos
    • , Lu Yu
    •  & Jörg Mansfeld

  • Article
    | Open Access

    Staphylococcal pathogens adhere to their human targets using adhesins, which can withstand extremely high forces. Here, authors use single-molecule force spectroscopy to determine the similarly high unfolding forces of B domains that link the adhesin to the bacterium.

    • Lukas F. Milles
    • , Eduard M. Unterauer
    •  & Hermann E. Gaub

  • Article
    | Open Access

    Uptake and release of glycerol from the small intestine and adipocytes is facilitated by a subclass of aquaporins (AQP), but how glycerol flow is regulated remains poorly understood. Here authors solve the crystal structure of AQP10 and show how lipolysis is coupled to AQP10 regulation in

    • Kamil Gotfryd
    • , Andreia Filipa Mósca
    •  & Pontus Gourdon

  • Article
    | Open Access

    [FeFe]-hydrogenases catalyze H2-evolution and -oxidation at very high turnover-rates. Here the authors provide experimental evidence for the proposed proton-transfer (PT) pathway by kinetically, spectroscopically, and crystallographically characterizing eleven mutants from the two [FeFe]-hydrogenases CpI and HydA1.

    • Jifu Duan
    • , Moritz Senger
    •  & Martin Winkler

  • Article
    | Open Access

    Signalling through the endothelin receptor ETB, a class A GPCR, induces nitric oxide-mediated vasorelaxation. Here the authors present the crystal structures of the human ETB receptor bound to the peptide hormone endothelin-3 and in complex with the ETB-selective partial agonist IRL1620 and discuss mechanistic implications for receptor activation.

    • Wataru Shihoya
    • , Tamaki Izume
    •  & Osamu Nureki

  • Article
    | Open Access

    Group II introns are large, self-splicing RNAs that catalyze their own excision from pre-mRNA molecules. Here the authors determine the 3.7 Å crystal structure of the group II intron in the stage immediately before the second step of splicing and present a complete model for the second step of group II intron splicing.

    • Russell T. Chan
    • , Jessica K. Peters
    •  & Navtej Toor

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