Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    Plexins are the receptors for the guidance molecules semaphorins and regulate immunity and the development of the nervous and cardiovascular systems. Here authors present a structure of full-length human PlexinC1 in complex with its ligand A39R, which reveals how inter-domain interactions couple extracellular ligand binding to receptor activation and signaling.

    • Yi-Chun Kuo
    • , Hua Chen
    •  & Xuewu Zhang

  • Article
    | Open Access

    The mechanisms of action of proteasome inhibitors (PI) in multiple myeloma (MM) treatment are not fully elucidated. Here, the authors use unbiased phosphoproteomics in PI-treated MM and show increased phosphorylation of splicing-associated proteins, ultimately revealing splicing interference as a mode of PI action as well as demonstrating the spliceosome as a specific therapeutic vulnerability in this disease.

    • Hector H. Huang
    • , Ian D. Ferguson
    •  & Arun P. Wiita

  • Article
    | Open Access

    MicroRNA genes are transcribed to long primary transcripts called primary microRNAs, which are cleaved by Microprocessor. Here the authors employ high-throughput sequencing and Microprocessor assay to show that mismatches and wobble base pairs in primary microRNAs affect the accuracy and efficiency of Microprocessor processing.

    • Shaohua Li
    • , Trung Duc Nguyen
    •  & Tuan Anh Nguyen

  • Article
    | Open Access

    The mHsp60-mHsp10 chaperonin system forms alternating single and double ring complexes to assist protein folding, but the molecular details of this cycle are not fully understood. Here, the authors present cryoEM and crystal structures of key intermediates of the mHsp60-mHsp10 reaction cycle.

    • Yacob Gomez-Llorente
    • , Fady Jebara
    •  & Iban Ubarretxena-Belandia

  • Article
    | Open Access

    Rhodobacter capsulatus NAD+ dependent formate dehydrogenase (RcFDH) is a molybdoenzyme that catalyses the reversible oxidation of formate to carbon dioxide, and is of interest for biotechnological applications. Here the authors present the cryo-EM structures of RcFDH as isolated from R. capsulatus and in the reduced state with bound NADH, and discuss the enzyme mechanism.

    • Christin Radon
    • , Gerd Mittelstädt
    •  & Petra Wendler

  • Article
    | Open Access

    Peptide-MHC (pMHC) tetramers are important tools for probing T cell repertoire and adaptive immune responses. Here the authors use a molecular chaperone, TAPBPR, to develop a high-throughput, multiplexible platform for pMHC tetramer generation to facilitate simultaneous assessments of T cell repertoire/antigen specificity and transcriptome.

    • Sarah A. Overall
    • , Jugmohit S. Toor
    •  & Nikolaos G. Sgourakis

  • Article
    | Open Access

    Halogenated plant natural products are rare and plant halogenation enzymes are thus far unknown. Here Kim et al. identify a dechloroacutumine halogenase from Common Moonseed that catalyzes the final chlorination step in the biosynthesis of acutumine, a chloroalkaloid with selective cytotoxicity to cultured T cells.

    • Colin Y. Kim
    • , Andrew J. Mitchell
    •  & Jing-Ke Weng

  • Article
    | Open Access

    Trypanosoma brucei guanosine 5′-monophosphate reductase (TbGMPR) catalyses the conversion of GMP to inosine 5′-monophosphate and contains a cystathionine-β-synthase (CBS) domain. Here the authors combine X-ray crystallography and kinetic measurements and present the GMP-, GTP-bound and nucleotide-free TbGMPR structures and show that guanine and adenine nucleotides are allosteric regulators of TbGMPR that bind to the CBS domain.

    • Akira Imamura
    • , Tetsuya Okada
    •  & Takashi Inui

  • Article
    | Open Access

    Some transcription factors have been proposed to functionally interact with RNA to facilitate proper regulation of gene expression. Here the authors demonstrate that human Sox2 interact directly and with high affinity to RNAs through its HMG DNA-binding domain.

    • Zachariah E. Holmes
    • , Desmond J. Hamilton
    •  & Robert T. Batey

  • Article
    | Open Access

    Obesity predisposes to type 2 diabetes, but the mechanisms of obesity-associated β cell dysfunction are incompletely understood. Here the authors report that obesity increases the levels of miR-802, which impairs insulin transcription and secretion by targeting NeuroD1 and Fzd5.

    • Fangfang Zhang
    • , Dongshen Ma
    •  & Liang Jin

  • Article
    | Open Access

    The local X-ray-induced dynamics that occur in protein crystals during serial femtosecond crystallography (SFX) measurements at XFELs are not well understood. Here the authors performed a time-resolved X-ray pump X-ray probe SFX experiment, and they observe distinct structural changes in the disulfide bridges and peptide backbone of proteins; complementing theoretical approaches allow them to further characterize the details of the X-ray induced ionization and local structural dynamics.

    • Karol Nass
    • , Alexander Gorel
    •  & Ilme Schlichting

  • Article
    | Open Access

    Mass photometry is a label-free optical approach capable of detecting, imaging and accurately measuring the mass of single biomolecules in solution. Here, the authors demonstrate the potential of mass photometry for quantitatively characterizing sample heterogeneity of purified protein complexes with implications for structural studies specifically and in vitro studies more generally.

    • Adar Sonn-Segev
    • , Katarina Belacic
    •  & Philipp Kukura

  • Article
    | Open Access

    The Legionella effector MavC catalyses the ubiquitination of the E2 enzyme UBE2N in the host cell through a transglutamination reaction, which can be inhibited by the Legionella effector Lpg2149. Here, the authors provide mechanistic insights into these processes by determining the crystal structures of the MavC/UBE2N/Ub ternary complex, the MavC/UBE2N-Ub product complex and the MavC/Lpg2149 complex.

    • Yajuan Mu
    • , Yue Wang
    •  & Yue Feng

  • Article
    | Open Access

    Protein aggregation remains a significant challenge for manufacturing of protein biopharmaceuticals. Here, the authors demonstrate the use of directed evolution and an assay for in vivo innate protein aggregation-propensity to generate aggregation-resistant scFv fragments.

    • Jessica S. Ebo
    • , Janet C. Saunders
    •  & David J. Brockwell

  • Article
    | Open Access

    RNA is implicated in the targeting and function of Polycomb Group (PcG) chromatin regulators. Here the authors show that R-loops, three-stranded nucleic acid structures formed by DNA and RNA, are formed at some PcG binding sites in flies, as they are in mammals. Fly PRC2 can drive formation of RNA-DNA hybrids in vitro.

    • Célia Alecki
    • , Victoria Chiwara
    •  & Nicole J. Francis

  • Article
    | Open Access

    Identifying mutation-derived neoantigens by proteogenomics requires robust strategies for quality control. Here, the authors propose peptide retention time as an evaluation metric for proteogenomics quality control methods, and develop a deep learning algorithm for accurate retention time prediction.

    • Bo Wen
    • , Kai Li
    •  & Bing Zhang

  • Article
    | Open Access

    Energy coupling factor (ECF) transporters are responsible for the uptake of micronutrients and consist of an integral membrane unit, the S-component, which confers substrate specificity. Here, authors present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter.

    • Ignacio Faustino
    • , Haleh Abdizadeh
    •  & Siewert J. Marrink

  • Article
    | Open Access

    The formation of C-C bonds in fatty acid and polyketide biosynthesis depends on β-ketoacyl-acyl carrier protein (ACP) synthases (KSs). Here, the authors present structures of E.coli KSs bound to substrate mimetic bearing ACPs, providing insights into the catalytic mechanism underlying C-C bond forming reactions.

    • Jeffrey T. Mindrebo
    • , Ashay Patel
    •  & Michael D. Burkart

  • Article
    | Open Access

    Identifying kinases responsible for specific phosphorylation events remains challenging. Here, the authors leverage kinase inhibitor profiles for the identification of kinase-substrate site pairs in cell extracts, developing a method that can identify the enzymes responsible for unassigned phosphorylation events.

    • Nikolaus A. Watson
    • , Tyrell N. Cartwright
    •  & Jonathan M. G. Higgins

  • Article
    | Open Access

    RNA sequence-structure-function relationships can be studied via assays of variant activity. The authors developed a method to systematically determine ribozyme variant kinetics, using it to map double-mutant interactions and show that cleavage rate drives sequence conservation in the glmS ribozyme.

    • Johan O. L. Andreasson
    • , Andrew Savinov
    •  & William J. Greenleaf

  • Article
    | Open Access

    The mechanisms of Z-ring assembly and regulation in bacteria are poorly understood, particularly in non-model organisms. Here, Sogues et al. study the interaction between FtsZ and SepF in Corynebacterium glutamicum, showing an essential interdependence of these proteins for formation of a functional Z-ring.

    • Adrià Sogues
    • , Mariano Martinez
    •  & Pedro M. Alzari

  • Article
    | Open Access

    Translational control of gene expression can lead to significant divergence between mRNA and protein abundance. Here, the authors describe transcriptional rewiring and translational buffering during transition from naïve to primed pluripotency through quantitation of mRNA-abundance, translation rate and protein expression.

    • Yaser Atlasi
    • , Seyed Mehdi Jafarnejad
    •  & Hendrik G. Stunnenberg

  • Article
    | Open Access

    The molecular basis of activin receptor-like kinase 1 (ALK1)-mediated endothelial bone morphogenetic protein (BMP) signalling is not fully understood. Here, the authors present crystal structures of the BMP10:ALK1 and prodomain-bound BMP9:ALK1 complexes, providing mechanistic insights into ALK1 signalling specificity.

    • Richard M. Salmon
    • , Jingxu Guo
    •  & Wei Li

  • Article
    | Open Access

    How nature creates 1,2,3-triazole ring is a relevant question to N-N bond biosynthesis. Here, the authors report the biosynthetic route to the triazole-bearing antimetabolite 8-azaguanine and reveal that this can be assembled through an enzymatic and non-enzymatic cascade, in which nitric oxide is used as a building block.

    • Guiyun Zhao
    • , Yuan-Yang Guo
    •  & Yi-Ling Du

  • Article
    | Open Access

    Asparaginyl endopeptidases (AEPs) catalyze the cyclization step during the biosynthesis of cyclic peptides in plants. Here, the authors report a recombinantly produced AEP that catalyzes the backbone cyclization of a linear cyclotide precursor and an engineered analog with high efficiency and in a pH-dependent manner.

    • Junqiao Du
    • , Kuok Yap
    •  & David J. Craik

  • Article
    | Open Access

    Upon target RNA recognition, type III CRISPR-Cas systems produce cyclic oligoadenylates that activate effectors such as Csm6 ribonucleases. Here, Garcia-Doval et al. show that Enteroccocus italicus Csm6 degrades its cyclic hexa-AMP activator, and report the crystal structure of the protein bound to an activator mimic.

    • Carmela Garcia-Doval
    • , Frank Schwede
    •  & Martin Jinek

  • Article
    | Open Access

    Data-independent acquisition-mass spectrometry (MS) typically requires many preparatory MS runs to produce experiment-specific spectral libraries. Here, the authors show that empirical correction of in silico predicted spectral libraries enables efficient generation of high-quality experiment-specific libraries.

    • Brian C. Searle
    • , Kristian E. Swearingen
    •  & Mathias Wilhelm

  • Article
    | Open Access

    Exercise has been shown to be an effective approach to ameliorate metabolic disease in mice housed at ambient temperatures, a condition of mild cold stress to mice. Here the authors show that molecular and metabolic adaptations to exercise are blunted when mice are housed in thermoneutral conditions.

    • Steffen H. Raun
    • , Carlos Henriquez-Olguín
    •  & Lykke Sylow

  • Article
    | Open Access

    Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. Here, the authors use single-molecule assays to examine the mechanism of action of CHD4 remodeller, and provide evidence that CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation.

    • Yichen Zhong
    • , Bishnu P. Paudel
    •  & Joel P. Mackay

  • Article
    | Open Access

    Acyl-acyl carrier protein reductase (AAR) and aldehyde deformylating oxygenase (ADO) are the two enzymes in a cyanobacterial alkane biosynthesis pathway that is of interest for biofuel production. Here the authors provide insights into the catalytic mechanisms of AAR and the coupling between the two enzymes by determining the crystal structures of AAR alone and three AAR–ADO complexes with various bound ligands.

    • Yu Gao
    • , Hongmei Zhang
    •  & Mei Li

  • Article
    | Open Access

    Robo3 is a divergent, multifunctional member of the Robo receptor family that mediates axon guidance by its ligand NELL2 instead of the canonical Slit ligands. Here, the authors present the crystal structures of human Robo3 in complex with NELL1 and NELL2, and they show through biophysical and functional assays how NELL-Robo3 affinity and ligand-induced receptor multimerization control axon guidance activity.

    • Joseph S. Pak
    • , Zachary J. DeLoughery
    •  & Engin Özkan

  • Article
    | Open Access

    Heparan sulfates (HS) contain functionally relevant structural motifs, but determining their monosaccharide sequence remains challenging. Here, the authors develop an ion mobility mass spectrometry-based method that allows unambiguous characterization of HS sequences and structure-activity relationships.

    • Rebecca L. Miller
    • , Scott E. Guimond
    •  & Kevin Pagel

  • Article
    | Open Access

    Mfd recognizes stalled transcriptional complexes at sites of lesions and recruits the nucleotide excision repair proteins (UvrAB) to the site. Here the authors use live cell imaging in E. coli to demonstrate that coordinated ATP hydrolysis by UvrA and loading of UvrB on DNA facilitate the dissociation of Mfd from the handoff complex.

    • Han Ngoc Ho
    • , Antoine M. van Oijen
    •  & Harshad Ghodke

  • Article
    | Open Access

    SNX-BAR proteins are a family of PX and BAR domain-containing proteins with pivotal roles in trafficking processes. Here authors present the cryo-EM structure of the full-length fungal SNX-BAR Mvp1, which is an autoinhibited tetramer and provides critical insight into SNX-BAR function and regulation.

    • Dapeng Sun
    • , Natalia V. Varlakhanova
    •  & Marijn G. J. Ford

  • Article
    | Open Access

    The ribosome-associated complex (RAC), which contains the Hsp40 protein Zuo1 and the non-canonical Hsp70 protein Ssz1 forms a chaperone triad with the fungal-specific Hsp70 protein Ssb. Here the authors combine X-ray crystallography, crosslinking and biochemical experiments and present the structure of the Zuo1 N-terminus bound to Ssz1 and demonstrate that Ssz1 is an active chaperone for nascent chains.

    • Ying Zhang
    • , Genís Valentín Gesé
    •  & Irmgard Sinning

  • Article
    | Open Access

    Kucha is a rare variety of tea tree that produces the non-stimulatory theacrine instead of caffeine. Here the authors show that theacrine synthase from Kucha has N9-methyltransferase activity resulting from amino acid substitutions that explain substrate specificity and could potentially guide production of caffeine-free tea.

    • Yue-Hong Zhang
    • , Yi-Fang Li
    •  & Rong-Rong He

  • Article
    | Open Access

    O-alkylation of carboxylates by alkyl halides has only been observed transiently in enzymatic processes. Here, the authors show a carboxylate alkylating enzyme, BrtB, that catalyzes C-O bond formation between free fatty acids and secondary alkyl chlorides.

    • João P. A. Reis
    • , Sandra A. C. Figueiredo
    •  & Pedro N. Leão

  • Article
    | Open Access

    Acetaldehyde–alcohol dehydrogenase (AdhE) converts acetyl-CoA to ethanol and is a key enzyme in bacterial alcoholic fermentation. AdhE forms spirosomes and, here, the authors present the cryoEM structures of compact and extended E.coli AdhE spirosomes and show that the extended conformation is the catalytically active form of the enzyme and discuss mechanistic implications.

    • Pauline Pony
    • , Chiara Rapisarda
    •  & Rémi Fronzes

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