Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    Cellobiohydrolases (CBHs) are critical for natural and industrial biomass degradation but their structure–activity relationships are not fully understood. Here, the authors present the biochemical and structural characterization of two CBHs, identifying protein regions that confer enhanced CBH activity.

    • Larry E. Taylor II
    • , Brandon C. Knott
    •  & Gregg T. Beckham

  • Article
    | Open Access

    Polycystic kidney disease 2-like 1 protein (PKD2L1) is a voltage-dependent calcium-dependent nonselective ion channel involved in sour taste perception and regulation of pH-dependent action potential of spinal cord neurons. Here the authors present the 3.4 Å cryo-EM structure of PKD2L1 in the open state and propose a model for the gating mechanism.

    • Qiang Su
    • , Feizhuo Hu
    •  & Tingliang Wang

  • Article
    | Open Access

    CesT is a type III secretion system chaperone that interacts with the post-transcriptional regulator CsrA, which is important for the modulation of post-attachment signaling in enteropathogenic and enterohemorrhagic Escherichia coli. Here the authors present the structure of the CsrA/CesT complex and propose a mechanism for CsrA-modulation by CesT.

    • Fei Ye
    • , Fanli Yang
    •  & Guangwen Lu

  • Article
    | Open Access

    Heat capacity changes affect the temperature dependence of enzyme catalysis, with implications for thermoadaptation, however their physical basis is unknown. Here the authors show that heat capacity changes are calculable by simulation, revealing distinct dynamical contributions from regions remote from the active site.

    • Marc W. van der Kamp
    • , Erica J. Prentice
    •  & Vickery L. Arcus

  • Article
    | Open Access

    Deubiquitinases are proteases that cleave after the C-terminus of ubiquitin to hydrolyze ubiquitin chains and cleave ubiquitin from substrates. Here the authors describe a reactive-site-centric chemoproteomics approach to studying deubiquitinase activity, and expand the repertoire of known deubiquitinases.

    • David S. Hewings
    • , Johanna Heideker
    •  & Ingrid E. Wertz

  • Article
    | Open Access

    Jumonji-C domain containing protein 5 (JMJD5) is essential for animal development but its catalytic activity has remained elusive so far. Here the authors show that human JMJD5 is an arginyl-hydroxylase and present the cofactor, substrate and product bound JMJD5 crystal structures.

    • Sarah E. Wilkins
    • , Md. Saiful Islam
    •  & Rasheduzzaman Chowdhury

  • Article
    | Open Access

    The catalytic activity of dioxygenase AsqJ is strictly relying on the methylation of quinolone substrates. Here, the authors apply molecular simulations, X-ray crystallography and in vitro biochemical studies to the engineering of dioxygenase AsqJ with improved catalytic activity for modified non-methylated surrogates.

    • Sophie L. Mader
    • , Alois Bräuer
    •  & Ville R. I. Kaila

  • Article
    | Open Access

    Undecaprenyl pyrophosphate phosphatase (UppP) recycles the lipid carrier essential for bacterial cell wall synthesis. Here authors present the crystal structure of UppP from E. coli at 2.0 Å resolution, which sheds light on its phosphatase mechanism and indicates a potential flippase role for UppP.

    • Sean D. Workman
    • , Liam J. Worrall
    •  & Natalie C. J. Strynadka

  • Article
    | Open Access

    The decapping enzyme Dcp2 removes the 5′ eukaryotic cap from mRNA transcripts and acts in concert with its essential activator Dcp1 and various coactivators. Here the authors present the structure of the fully-activated mRNA decapping complex, which reveals how Dcp2 recognizes the cap substrate and coactivators Edc1 and Edc3 activate catalysis.

    • Jeffrey S. Mugridge
    • , Ryan W. Tibble
    •  & John D. Gross

  • Article
    | Open Access

    BldC regulates the onset of differentiation in Streptomycetes by a yet unknown molecular mechanism. Using a combination of structural, biochemical and in vivo approaches, the authors show that BldC controls the transcription of several developmental regulators and unravel its DNA binding mode.

    • Maria A. Schumacher
    • , Chris D. den Hengst
    •  & Mark J. Buttner

  • Article
    | Open Access

    The molecular mechanisms that define the periodicity or rate of the circadian clock are not well understood. Here the authors use a multidisciplinary approach and identify a mechanism for period regulation that depends on the affinity of the core clock proteins for one another.

    • Clark Rosensweig
    • , Kimberly A. Reynolds
    •  & Carla B. Green

  • Article
    | Open Access

    Disruption of the ubiquitin proteasome system (UPS) is often associated with neurodegenerative diseases. Here the authors demonstrate the existence of a general mechanism of proteasomal impairment triggered by a specific protein oligomer structure, irrespective of its protein constituent.

    • Tiffany A. Thibaudeau
    • , Raymond T. Anderson
    •  & David M. Smith

  • Article
    | Open Access

    Homologous recombination (HR) typically uses DNA as a donor template to accurately repair DNA breaks. Here, the authors elucidate two mechanisms by which RAD52 uses RNA as a template for HR: one involving RNA-mediated synapsis of a homologous DNA break, and the other involving reverse transcriptase dependent RNA-to-DNA sequence transfer at DNA breaks.

    • Shane McDevitt
    • , Timur Rusanov
    •  & Richard T. Pomerantz

  • Article
    | Open Access

    Teneurins are cell-cell adhesion receptors that evolved through horizontal gene transfer in which a bacterial YD-repeat protein fused to a eukaryotic receptor. Here the authors present crystallographic and cryo-EM structures of two Teneurins, revealing an ancient YD-repeat protein super-fold.

    • Verity A. Jackson
    • , Dimphna H. Meijer
    •  & Elena Seiradake

  • Article
    | Open Access

    Polysaccharides are the primary structural cell wall and energy storage molecules of seaweed. Here, the authors show how the geographically restricted dietary polysaccharide agarose is selectively utilized by the human intestinal bacterium Bacteroides uniformis, providing insight into how carbohydrate metabolism evolves within the human microbiome.

    • Benjamin Pluvinage
    • , Julie M. Grondin
    •  & D. Wade Abbott

  • Article
    | Open Access

    Glycoprotein G of vesicular stomatitis virus (VSV) enables viral entry by binding to the major VSV receptor LDL-R. Here the authors present crystal structures of G in complex with two distinct CR domains of LDL-R, identifying structural determinants for VSV infectivity in mammalian and insect cells.

    • Jovan Nikolic
    • , Laura Belot
    •  & Aurélie A. Albertini

  • Article
    | Open Access

    Optimizing an enzyme usually requires testing thousands of variants, thus consuming large amounts of material and time. Here, the authors present a method that allows for measuring two different activities of the same enzyme simultaneously instead of doing two consecutive rounds of screening.

    • Fuqiang Ma
    • , Meng Ting Chung
    •  & Guang-Yu Yang

  • Article
    | Open Access

    An integrated network of chaperones and protein degradation machineries called the proteostasis network (PN) is required to maintain protein homeostasis. Here the authors show that one of the components of the PN, the chaperonin TRiC, interacts with the core transcription-coupled nucleotide excision repair protein CSA to ensure its assembly into the CRLCSA complex.

    • Alex Pines
    • , Madelon Dijk
    •  & Haico van Attikum

  • Article
    | Open Access

    During asymmetric divisions fate determinants and niche contacts segregate unequally between daughter cells, but the mechanism is unclear. Here the authors show that Insc:LGN tetramers promote assembly of Par3-Insc-LGN-GαiGDP complexes and asymmetric fate specification independently of microtubule motors.

    • Simone Culurgioni
    • , Sara Mari
    •  & Marina Mapelli

  • Article
    | Open Access

    Riboswitches are RNA-based regulatory elements, which regulate downstream gene expression by binding of small molecular weight ligands. Here the authors demonstrate the molecular mechanism of a transcriptional riboswitch that integrates changes in transcription rates, metabolite concentration, and kinetic on- and off-rates of ligand binding.

    • Christina Helmling
    • , Dean-Paulos Klötzner
    •  & Harald Schwalbe

  • Article
    | Open Access

    The underlying regulatory mechanisms of phytoplankton assimilation and microbial oxidation of ammonium in the surface ocean are unclear. Here, using isotope labeling experiments, the authors show that ambient nitrate is a key variable bifurcating ammonium flow through assimilation or oxidation.

    • Xianhui Sean Wan
    • , Hua-Xia Sheng
    •  & Shuh-Ji Kao

  • Article
    | Open Access

    Na+-coupled acid-base membrane transport proteins regulate blood pressure, ion homeostasis and acid-base chemistry. Here the authors present the 3.9 Å resolution cryoEM structure of the sodium-bicarbonate cotransporter NBCe1 and characterize its ion coordination site and ion accessibility pathway with mutagenesis experiments.

    • Kevin W. Huynh
    • , Jiansen Jiang
    •  & Ira Kurtz

  • Article
    | Open Access

    Despite being highly toxic, carbon monoxide (CO) is also essential as an intracellular signalling molecule, but CO-dependent signalling is poorly understood. Here, authors employ spectroscopic and electrophysiology methods and find that CO activates KATP channels via SUR2A, a heme-regulated receptor.

    • Sofia M. Kapetanaki
    • , Mark J. Burton
    •  & Emma Raven

  • Article
    | Open Access

    MANF is a secreted ER stress-inducible protein that protects neurons, pancreatic β cells and cardiomyocytes from cell death under oxidative stress, hypoxic or ischemic conditions. Here the authors show that MANF confers cytoprotection through direct binding to sulfatide followed by cellular uptake in both C. elegans and mammalian cells.

    • Meirong Bai
    • , Roman Vozdek
    •  & Dengke K. Ma

  • Article
    | Open Access

    There is growing evidence that the kinetics of interactions between inhibitors and their targets can strongly impact therapeutic efficacy. Here the authors describe an isothermal titration calorimetry-based method that can rapidly quantify inhibition kinetics and measure sub-nM binding affinities.

    • Justin M. Di Trani
    • , Stephane De Cesco
    •  & Anthony K. Mittermaier

  • Article
    | Open Access

    Aggregation is sequence-specific and nucleated by short aggregating protein segments (APR). Here authors use a multidisciplinary approach to show that in E.coli some frequently occurring APRs lead to protein aggregation and ultimately bacterial cell death, which could serve as antibacterial strategy.

    • Ladan Khodaparast
    • , Laleh Khodaparast
    •  & Joost Schymkowitz

  • Article
    | Open Access

    Poly(ADP-ribose) polymerases (PARPs) catalyse ADP-ribose posttranslational modifications using NAD+ as a substrate. Here, the authors present the crystal structure of PARP-1 bound to the non-hydrolyzable NAD+ analog BAD and provide insights into the mechanism of PARP-1 allosteric regulation.

    • Marie-France Langelier
    • , Levani Zandarashvili
    •  & John M. Pascal

  • Article
    | Open Access

    The human type 1 insulin-like growth factor receptor (IGF-1R) is important for normal human growth and development. Here, the authors present the crystal structures of the IGF-1R ectodomain both in its apo form and in complex with its ligand insulin-like growth factor I and discuss the receptor activation mechanism.

    • Yibin Xu
    • , Geoffrey K.-W. Kong
    •  & Michael C. Lawrence

  • Article
    | Open Access

    Deubiquitinating enzymes (DUBs) are essential to modulate ubiquitin signaling. While known DUBs can be grouped into six families, the authors here present biochemical and structural evidence for a seventh DUB family, defining determinants of substrate specificity for two representative enzymes.

    • Thomas Hermanns
    • , Christian Pichlo
    •  & Kay Hofmann

  • Article
    | Open Access

    LPMOs catalyze the oxidative breakdown of polysaccharides, thereby facilitating biomass degradation. By analyzing the digestive proteome of firebrats, the authors here identify a yet uncharacterized LPMO family and provide phylogenetic, structural and biochemical insights into its origin and functions.

    • Federico Sabbadin
    • , Glyn R. Hemsworth
    •  & Simon J. McQueen-Mason

  • Article
    | Open Access

    Calcium-independent phospholipase A2β (iPLA2β) is involved in many physiological and pathological processes but the underlying mechanisms are largely unknown. Here, the authors present the structure of dimeric iPLA2β, providing insights into the regulation of its activity and cellular localization.

    • Konstantin R. Malley
    • , Olga Koroleva
    •  & Sergey Korolev

  • Article
    | Open Access

    Polarized localization of Numb and Pon in Drosophila neuroblasts (NBs) enables their unequal segregation during asymmetric cell divisions. Here, the authors demonstrate liquid-liquid phase separation of Pon and Numb in NBs mediated by multivalent intermolecular interactions is required for their basal condensation.

    • Zelin Shan
    • , Yuting Tu
    •  & Wenyu Wen

  • Article
    | Open Access

    NaK is a non-selective cation channel that conducts sodium (Na+) and potassium (K+) equally well. Here authors use ssNMR and MD simulations to show that the selectivity filter of NaK adopts two conformations in the absence of ions, one of which is preferred by Na+ and the other by K+.

    • Chaowei Shi
    • , Yao He
    •  & Han Sun

  • Article
    | Open Access

    Amyloid fibril structures can display polymorphism. Here the authors reveal the cryo-EM structures of several different fibril morphologies of a peptide derived from an amyloidogenic immunoglobulin light chain and present a mathematical analysis of physical factors that influence fibril polymorphism.

    • William Close
    • , Matthias Neumann
    •  & Marcus Fändrich

  • Article
    | Open Access

    Microrchidia CW-type zinc finger protein 2 (MORC2) is an effector of epigenetic silencing by the human silencing hub (HUSH). Here the authors present the crystal structures of MORC2 and disease-causing MORC2 mutants and give mechanistic insights into how MORC2 mediates HUSH-dependent silencing.

    • Christopher H. Douse
    • , Stuart Bloor
    •  & Yorgo Modis

  • Article
    | Open Access

    Many aptamer-fluorophore complexes suffer from low quantum yield and low extinction coefficients limiting their usability. Here the authors isolate new Mango aptamers with improved fluorescent properties for both fixed and live-cell imaging by using competitive ligand binding microfluidic selection.

    • Alexis Autour
    • , Sunny C. Y. Jeng
    •  & Peter J. Unrau

  • Article
    | Open Access

    Tools to investigate a wide range of 3D microenvironmental parameters are important for understanding and controlling cell fate. Here, the authors develop hydrogels with orthogonal biochemical gradients and use this screening system to identify microenvironments that induce mesenchymal stem cell chondrogenesis.

    • Sebastián L. Vega
    • , Mi Y. Kwon
    •  & Jason A. Burdick

  • Article
    | Open Access

    The core of the telomerase holoenzyme is composed of the reverse transcriptase and the non-coding RNA template. Here the authors identify Pof8 as a new constitutive component of fission yeast telomerase, loss of which causes telomerase assembly defects and critically short telomeres.

    • Diego J. Páez-Moscoso
    • , Lili Pan
    •  & Peter Baumann

  • Article
    | Open Access

    The telomerase holoenzyme is minimally composed of the reverse transcriptase and the RNA template. Here the authors identify Lar7 as a member of the full complex that helps to stabilise it and protect telomerase RNA from degradation.

    • Laura C. Collopy
    • , Tracy L. Ware
    •  & Kazunori Tomita

  • Article
    | Open Access

    In meso crystallization of membrane proteins is limited to proteins with small extracellular domains (ECDs). Here, authors combine monoacylglycerols and phospholipids to design stable ultra-swollen bicontinuous cubic phases that allow in meso crystallization of proteins with large ECDs.

    • Alexandru Zabara
    • , Josephine Tse Yin Chong
    •  & Raffaele Mezzenga

  • Article
    | Open Access

    Cationic amino acid transporters (CATs) belong to the physiologically important solute carrier (SLC) 7 family. Here, the authors present the structure of the mammalian CAT transporter homologue Geobacillus kaustophilus GkApcT, which reveals how arginine is recognized, and propose a model for proton-coupled amino acid transport.

    • Katharina E. J. Jungnickel
    • , Joanne L. Parker
    •  & Simon Newstead

  • Article
    | Open Access

    Heterotopic ossification (HO) is a painful disease of unknown etiology characterized by extraskeletal bone formation after injury. Here the authors show that TGF-β is increased in HO lesions, where it promotes the early stages of HO pathology, and demonstrate that TGF-β inhibition ameliorates HO in mice.

    • Xiao Wang
    • , Fengfeng Li
    •  & Xu Cao

  • Article
    | Open Access

    The number of tRNA isodecoders has expanded significantly during evolution, which has resulted in ambiguity in tRNA selection by synthetases. Here the authors identify and characterize a dedicated proofreading factor that eliminates errors caused by ambiguity in tRNA selection by eukaryotic tRNA synthetases.

    • Santosh Kumar Kuncha
    • , Mohd Mazeed
    •  & Rajan Sankaranarayanan

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