Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    5-Deoxyribose is formed from 5′-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine enzymes. Here, the authors identify and biochemically characterize a bacterial salvage pathway for 5-deoxyribose, consisting of three enzymes, and solve the crystal structure of the key aldolase.

    • Guillaume A. W. Beaudoin
    • , Qiang Li
    •  & Andrew D. Hanson

  • Article
    | Open Access

    Members of the transient receptor potential (TRP) ion channels conduct cations into cells upon activation by a variety of signals. Here authors present the cryo-EM structure of TRPC4 in its unliganded (apo) state, which provides molecular insights into TRPC4's ion selectivity and TPR channel evolution.

    • Jingjing Duan
    • , Jian Li
    •  & Jin Zhang

  • Article
    | Open Access

    Type II DNA topoisomerases (Top2s) direct the passage of one DNA duplex through another, which is important for resolving DNA entanglements. Here the authors combine X-ray crystallography and MD simulations and present the structure of the human Top2 DNA-gate in an open conformation and discuss mechanistic implications.

    • Shin-Fu Chen
    • , Nan-Lan Huang
    •  & Nei-Li Chan

  • Article
    | Open Access

    Binding of eIF4E to the 5′ cap of mRNAs is a key early step in canonical translation initiation, but the requirement for eIF4E is not universal. Here the authors show that the eIF4G homolog DAP5 interacts with eIF3 to promote cap-dependent translation of a significant number of mRNA in an eIF4E-independent manner.

    • Columba de la Parra
    • , Amanda Ernlund
    •  & Robert J. Schneider

  • Article
    | Open Access

    Uptake of vitamin B12 is essential for many prokaryotes, but in most cases the membrane proteins involved are yet to be identified. Here, the authors use X-ray crystallography and spectroscopy to characterize BtuM, a predicted bacterial substrate-modifying vitamin B12 transporter.

    • S. Rempel
    • , E. Colucci
    •  & D. J. Slotboom

  • Article
    | Open Access

    The NLRP3 inflammasome is an important component of inflammatory responses, but how it is negatively regulated is still unclear. Here the authors show that post-translational modification of NLRP3 by sumoylation suppresses inflammasome activity, and that desumoylation of NLRP3 by the SENP6 and SENP7 proteases promotes NLRP3 activation.

    • Rachael Barry
    • , Sidonie Wicky John
    •  & Pascal Meier

  • Article
    | Open Access

    The Sortilin-related CNS-expressed receptor 2 (SorCS2)–proneurotrophin signaling system regulates neuronal plasticity and its dysfunction is linked to schizophrenia. Here the authors present the structures of the SorCS2 ectodomain alone and in complex with Nerve Growth Factor, which provides insights into SorCS2 ligand binding and signaling.

    • Nadia Leloup
    • , Lucas M. P. Chataigner
    •  & Bert J. C. Janssen

  • Article
    | Open Access

    CRISPR-guided cytidine deaminases, including BE3 (Base Editor 3) and Target-AID (activation-induced cytidine deaminase), can covert C:G base pairs to T:A at target site. Here, the authors generate missense mutations of mouse Psen1 gene and find BE3 has higher editing efficiency than Target-AID.

    • Hiroki Sasaguri
    • , Kenichi Nagata
    •  & Takaomi C. Saido

  • Article
    | Open Access

    The capsaicin receptor TRPV1 has been structurally characterized, but the capsaicin activation dynamics remain elusive. Here authors use fluorescent unnatural amino acid incorporation, computational modeling and Φ-analysis to derive the capsaicin-bound open state model and reveal the capsaicin induced conformational changes.

    • Fan Yang
    • , Xian Xiao
    •  & Jie Zheng

  • Article
    | Open Access

    While ChIP-exo is low noise and highly informative regarding genome-wide binding proteins, libraries are difficult to construct. Here the authors present a simplified ChIP-exo method for high-resolution detection of interactions.

    • Matthew J. Rossi
    • , William K. M. Lai
    •  & B. Franklin Pugh

  • Article
    | Open Access

    RNA instability may be a contributing factor in amyotrophic lateral sclerosis (ALS). Here the authors carry out genome-wide assessment of RNA synthesis and stability in cells derived from patients with C9orf72 ALS, sporadic ALS and healthy controls.

    • E. M. Tank
    • , C. Figueroa-Romero
    •  & S. J. Barmada

  • Article
    | Open Access

    Viridicatin is a fungal alkaloid. Here, the authors identify and characterize the cyclopenase that catalyzes the last step of its biosynthesis in Aspergillus nidulans, the conversion of cyclopenin to viridicatin, and find that the reaction proceeds via an unusual elimination mechanism.

    • Shinji Kishimoto
    • , Kodai Hara
    •  & Kenji Watanabe

  • Article
    | Open Access

    The human CST complex (CTC1-STN1-TEN1) is essential for telomere homeostasis. Here the authors dissect the roles of individual CST subunits in telomere length maintenance through regulation of telomerase-mediated G-strand synthesis and DNA polymerase-mediated C-strand synthesis in colon cancer cells.

    • Xuyang Feng
    • , Shih-Jui Hsu
    •  & Carolyn M. Price

  • Article
    | Open Access

    NifB is a key enzyme in the biosynthesis pathway of the nitrogenase FeMo cofactor. Here, the authors investigate the maturation of its iron-sulfur clusters by EPR and biochemical analyses, showing how individual precursor clusters participate in the formation of the final iron-sulfur cluster.

    • Lee A. Rettberg
    • , Jarett Wilcoxen
    •  & Yilin Hu

  • Article
    | Open Access

    N6-Methyladenosine (m6A) is a post-transcriptional RNA modification that modulates RNA structure through a destabilization of m6A base pairing. Here the authors use NMR and UV melting experiments and show that m6A can also stabilize m6A–U base pairs and global RNA structure when positioned adjacent to a 5ʹ bulge.

    • Bei Liu
    • , Dawn K. Merriman
    •  & Hashim M. Al-Hashimi

  • Article
    | Open Access

    The biosynthesis of the antitumour antibiotic CC-1065 includes formation of a cyclopropane. Here, the authors identify the two enzymes that work together to catalyze this reaction, a radical S-adenosyl-l-methionine enzyme and a methyltransferase, and propose a mechanism for the cyclopropanation.

    • Wen-Bing Jin
    • , Sheng Wu
    •  & Gong-Li Tang

  • Article
    | Open Access

    Cas12a is a RNA-guided DNA endonuclease whose detailed mechanisms of target searching and DNA cleavage remained unclear. Here authors use single-molecule fluorescence assays to show that Cas12a searches for their on-target site.

    • Yongmoon Jeon
    • , You Hee Choi
    •  & Sangsu Bae

  • Article
    | Open Access

    Computationally designed enzymes often show lower activity or stability than their natural counterparts. Here, the authors present an evolution-inspired method for automated enzyme design, creating stable enzymes with accurate active site architectures and wild-type-like activities.

    • Gideon Lapidoth
    • , Olga Khersonsky
    •  & Sarel J. Fleishman

  • Article
    | Open Access

    Insulin promotes lipogenesis but, on the other hand, insulin resistance is associated with increased lipogenesis in the liver. Here the authors show that Snail1 is upregulated by insulin and inhibits lipogenesis by repressing Fasn expression but insulin-mediated Snail1 upregulation is impaired during obesity and insulin resistance.

    • Yan Liu
    • , Lin Jiang
    •  & Liangyou Rui

  • Article
    | Open Access

    Aspergillus fumigatus is a pathogenic fungus. Here the authors perform solid-state NMR measurements with intact Aspergillus cells, which provides insights into cell wall composition and dynamics and propose a structural model for fungal cell walls.

    • Xue Kang
    • , Alex Kirui
    •  & Tuo Wang

  • Article
    | Open Access

    Following double-strand break a cascade of events leads to the recruitment of repair factors to damaged sites. Here the authors identify ZNF506 as a key factor that mediates post-translational modification changes in H2AX affecting the DNA damage response.

    • Somaira Nowsheen
    • , Khaled Aziz
    •  & Zhenkun Lou

  • Article
    | Open Access

    Ubiquitin modification also occurs in archaea. Here, the authors characterize an archaeal ancestral ubiquitination system, present the crystal structure of the archaeal deubiquitinase Rpn11 from Caldiarchaeum subterraneum bound to ubiquitin and provide insights into evolutionary relationships.

    • Adrian C. D. Fuchs
    • , Lorena Maldoner
    •  & Jörg Martin

  • Article
    | Open Access

    The ability to produce homogeneous glycoproteins is expected to advance fundamental understanding in glycoscience, but current in vivo-based production systems have several limitations. Here, the authors develop an E. coli extract-based one-pot system for customized production of N-linked glycoproteins.

    • Thapakorn Jaroentomeechai
    • , Jessica C. Stark
    •  & Matthew P. DeLisa

  • Article
    | Open Access

    The kinesin-13 family of microtubule (MT) depolymerases are major regulators of MT dynamics. Here the authors provide insights into the MT depolymerization mechanism by solving the crystal structure of a kinesin-13 monomer (Kif2A) in complex with two bent αβ-tubulin heterodimers.

    • Daria Trofimova
    • , Mohammadjavad Paydar
    •  & John S. Allingham

  • Article
    | Open Access

    Human rotaviruses (RV) bind to histo-blood group antigens (HBGA) for attachment, but how different viral genotypes interact with HBGA isn’t known. Here, Hu et al. report crystal structures of a prevalent and a neonate-specific RV in complex with HBGA and provide insights into glycan recognition and age-restricted tropism of RVs.

    • Liya Hu
    • , Banumathi Sankaran
    •  & B. V. Venkataram Prasad

  • Article
    | Open Access

    DNA Ligase IV (LigIV) catalyzes nick sealing of DNA double-strand break substrates during non-homologous end-joining. Here the authors present the crystal structures of two human LigIV DNA-bound catalytic states, which provide insights into its catalytic mechanism and the molecular basis of LIG4 syndrome causing disease mutations.

    • Andrea M. Kaminski
    • , Percy P. Tumbale
    •  & Katarzyna Bebenek

  • Article
    | Open Access

    RNA–protein interactions often depend on the recognition of extended RNA elements but the identification of these motifs is challenging. Here, the authors present a global integrated approach to analyze RNA–protein binding landscapes, mapping extended RNA interaction motifs for four RNA-binding proteins.

    • Qin Zhou
    • , Nikesh Kunder
    •  & Zachary T. Campbell

  • Article
    | Open Access

    How the Early Earth transitioned from an abiotic world to the modern biogeochemical Earth system remains unclear. Here, the authors show that colonization of a minor fraction of Archean landmasses by topsoil bacteria would have been enough to match the modern land-to-ocean nitrogen export of ammonium and nitrate.

    • Christophe Thomazo
    • , Estelle Couradeau
    •  & Ferran Garcia-Pichel

  • Article
    | Open Access

    The Tousled-like kinase (TLKs) family belongs to a distinct branch of Ser/Thr kinases that exhibit the highest levels of activity during DNA replication. Here the authors present the crystal structure of the kinase domain from human TLK2 and propose an activation model for TLK2 based on biochemical and phosphoproteomics experiments.

    • Gulnahar B. Mortuza
    • , Dario Hermida
    •  & Guillermo Montoya

  • Article
    | Open Access

    Catabolizing lignin-derived aromatic compounds requires an aryl-O-demethylation step. Here the authors present the structures of GcoA and GcoB, a cytochrome P450-reductase pair that catalyzes aryl-O-demethylations and show that GcoA displays broad substrate specificity, which is of interest for biotechnology applications.

    • Sam J. B. Mallinson
    • , Melodie M. Machovina
    •  & John E. McGeehan

  • Article
    | Open Access

    The authors demonstrate a 3-tier mass spectrometry approach, including bottom-up and top-down proteomics, as well as native mass spectrometry to provide a detailed description of proteoforms, protein processing and post-translational modifications present within ribosomes from bacteria, plant, and human.

    • Michiel van de Waterbeemd
    • , Sem Tamara
    •  & Albert J. R. Heck

  • Article
    | Open Access

    The activation of dendritic cells (DC) is associated with a metabolic switch from oxidative to glycolytic metabolism. Here, the authors show that both strong and weak stimuli cause an immediate increase in glycolysis, but only strong stimuli induce long-term glycolytic reprogramming.

    • Hannah Guak
    • , Sara Al Habyan
    •  & Connie. M. Krawczyk

  • Article
    | Open Access

    RIPK3-mediated phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase is thought to be the trigger for MLKL activation during necroptotic signaling. Here the authors provide evidence that the transition of human MLKL from a monomeric state to a tetramer is essential for necroptosis signalling.

    • Emma J. Petrie
    • , Jarrod J. Sandow
    •  & James M. Murphy

  • Article
    | Open Access

    Asparaginyl endopeptidases (AEPs) are plant proteases that can also function as ligases, catalyzing the production of cyclic plant peptides. Here, the authors identify structural features that govern AEP ligase activity, providing insights to aid the discovery and engineering of ligase-type AEPs.

    • M. A. Jackson
    • , E. K. Gilding
    •  & D. J. Craik

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