Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    Cilia formation requires Intraflagellar transport (IFT) to move ciliary building blocks and signaling components into the cilium. Here authors use in vitro reconstitution and electron microscopy on IFT172 and reveal its ability to remodel large membrane surfaces into small vesicles.

    • Qianmin Wang
    • , Michael Taschner
    •  & Naoko Mizuno

  • Article
    | Open Access

    Guaianolides are pharmaceutically interesting molecules. Here, the authors isolate the enzyme kauniolide synthase from feverfew, show that it converts constunolide into a guaianolide via an unusual mechanism of action, and reconstruct the full kauniolide biosynthesis pathway in host organisms.

    • Qing Liu
    • , Arman Beyraghdar Kashkooli
    •  & Harro Bouwmeester

  • Article
    | Open Access

    Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

    • Marco Matejcic
    • , Edward J. Saunders
    •  & Christopher A. Haiman

  • Article
    | Open Access

    The Scotia Sea, located in the Southern Ocean, is a major hotspot for the drawdown of atmospheric CO2. Here, the authors show that the strength of the carbonate counter pump doubles when shelled pteropods dominate the plankton calcifier community, counteracting the amount of CO2 transferred to the deep ocean.

    • C. Manno
    • , F. Giglio
    •  & G. A. Tarling

  • Article
    | Open Access

    Mutating natural enzymes is effective in broadening the substrate or product range, but generally leads to reduced titers. Here the authors engineer hybrid polyketide synthases for efficient production of short-chain ketones from plant biomass hydrolysates in Streptomyces, which can increase the octane of gasoline.

    • Satoshi Yuzawa
    • , Mona Mirsiaghi
    •  & Jay D. Keasling

  • Article
    | Open Access

    The number of K+ occupied binding sites in the selectivity filter of potassium ion channels is still under debate. Here, the authors collect diffraction data on the K+ selective NaK channel NaK2K at a wavelength of 3.35 Å, close to the K absorption edge, revealing that all four binding sites in the selectivity filter are fully occupied by K+ ions.

    • Patricia S. Langan
    • , Venu Gopal Vandavasi
    •  & Leighton Coates

  • Article
    | Open Access

    Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca2+ levels to maintain cellular Ca2+ balance. Here the authors find that the STIM1 luminal domain monomer has multiple Ca2+ - binding sites which set the threshold for physiological activation of STIM1 in cells.

    • Aparna Gudlur
    • , Ana Eliza Zeraik
    •  & Patrick G. Hogan

  • Article
    | Open Access

    DNA methylation and H3K9 dimethylation are two linked epigenetic marks of silenced chromatin in plants that depend on the activity of CMT3/2 and SUVH4/5/6. Here the authors identify AGDP1 as an H3K9me2-binding protein required for heterochromatic non-CG DNA methylation, H3K9 dimethylation, and transcriptional silencing.

    • Cuijun Zhang
    • , Xuan Du
    •  & Jian-Kang Zhu

  • Article
    | Open Access

    The NDM-1 β-lactamase confers resistance to most β-lactam antibiotics. By functional analysis of residues required for hydrolysis, Sun et al. reveal stringent sequence constraints for carbapenems, suggesting that specific combinations of NDM-1 inhibitors might help reducing resistance development

    • Zhizeng Sun
    • , Liya Hu
    •  & Timothy Palzkill

  • Article
    | Open Access

    The protein tyrosine phosphatase SHP2 is a key regulator of cell cycle control. Here the authors combine NMR measurements and X-ray crystallography and show that wild-type SHP2 dynamically exchanges between a closed inactive conformation and an open activated form and that the oncogenic E76K mutation shifts the equilibrium to the open state, which is reversed by binding of the allosteric inhibitor SHP099.

    • Ricardo A. P. Pádua
    • , Yizhi Sun
    •  & Dorothee Kern

  • Article
    | Open Access

    The activity of several protein kinases is increased upon cellular production of reactive oxygen species, which can cause cysteine oxidation. Here the authors show that sulfenylation of specific cysteine residues within Src induce local structural changes that directly impact its activation.

    • David E. Heppner
    • , Christopher M. Dustin
    •  & Albert van der Vliet

  • Article
    | Open Access

    Activating mutations of the non-receptor protein tyrosine phosphatase SHP2 can cause cancer. Here the authors present the crystal structure of SHP2E76K, the most frequent cancer-associated SHP2 mutation, which adopts an open-state structure and show that the allosteric inhibitor SHP099 can revert SHP2E76K to its closed, autoinhibited conformation.

    • Jonathan R. LaRochelle
    • , Michelle Fodor
    •  & Stephen C. Blacklow

  • Article
    | Open Access

    Impaired kidney function can lead to an increase of β2-microglobulin (β2m) serum levels, which can cause β2m aggregation and amyloid fibril formation. Here the authors combine cryo-EM and magic angle spinning NMR measurements to determine the structure of a β2m fibril and they also present the low resolution model of a β2m fibril with a different morphology.

    • Matthew G. Iadanza
    • , Robert Silvers
    •  & Sheena E. Radford

  • Article
    | Open Access

    Proton pumping of mitochondrial complex I depends on the reduction of ubiquinone but the molecular mechanism of energy conversion is unclear. Here, the authors provide structural and biochemical evidence showing that movement of loop TMH1-2 in complex I subunit ND3 is required to drive proton pumping.

    • Alfredo Cabrera-Orefice
    • , Etienne Galemou Yoga
    •  & Ulrich Brandt

  • Article
    | Open Access

    Small interfering (siRNAs) can be toxic to cancer cells. Here the authors investigate the toxicity of microRNA in cancer cells by performing a siRNA screen that tests the miRNA activities of an extensive list of miRNAs with different 6mer seed sequences.

    • Quan Q. Gao
    • , William E. Putzbach
    •  & Marcus E. Peter

  • Article
    | Open Access

    Necroptotic cells activate MLKL and release inflammatory DAMPs, although the underlying regulatory mechanisms of this process are poorly understood. Here, Murai et al. develop a necroptosis-specific FRET sensor (SMART) that monitors MLKL membrane translocation to identify two modes of DAMP release.

    • Shin Murai
    • , Yoshifumi Yamaguchi
    •  & Hiroyasu Nakano

  • Article
    | Open Access

    Oncoprotein E6 facilitates the E6AP-catalyzed ubiquitination of p53. Here, the authors study the structural basis of this process by qualitative and quantitative cross-linking mass spectrometry, providing insights into E6AP-E6-p53 complex assembly and the conformational dynamics that enable p53 ubiquitination.

    • Carolin Sailer
    • , Fabian Offensperger
    •  & Florian Stengel

  • Article
    | Open Access

    Ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein that hydrolyzes both ATP and cGAMP. Here the authors present the crystal structures of the extracellular domain of mouse ENPP1 in complex with 3′3′-cGAMP and the reaction intermediate pA(3′,5′)pG and discuss mechanistic implications.

    • Kazuki Kato
    • , Hiroshi Nishimasu
    •  & Osamu Nureki

  • Article
    | Open Access

    Metal ions at the active site of an enzyme act as cofactors and their dynamic fluctuations might influence enzyme activity. Here authors use single-molecule FRET to study λ-exonuclease and find that metal-ion-coordination is correlated with enzymatic reaction-steps.

    • Wonseok Hwang
    • , Jungmin Yoo
    •  & Gwangrog Lee

  • Article
    | Open Access

    The autophagic receptor p62 recognizes arginylated (Nt-R) substrates through its ZZ domain (p62ZZ). Here the authors identify a p62 auto regulatory mechanism and provide structural insights into the selective recognition of Nt-R by p62ZZ and further show that Nt-R binding stimulates p62 oligomerization and macroautophagy.

    • Yi Zhang
    • , Su Ran Mun
    •  & Tatiana G. Kutateladze

  • Article
    | Open Access

    Additional sex combs-like (ASXLs) stimulate BAP1 deubiquitinase activity to induce tumor suppression, but how these complexes work in coordination in vivo is unclear. Here, the authors show the mutually reinforcing roles of BAP1 and ASXLs such that BAP1 promotes DEUBAD monoubiquitination of ASXL2, which in turn stimulates BAP1 DUB activity.

    • Salima Daou
    • , Haithem Barbour
    •  & El Bachir Affar

  • Article
    | Open Access

    Dimethyl fumarate (DMF) is a major drug in the treatment of psoriasis and multiple sclerosis. Here the authors reveal a mechanism of RSK/MSK inhibition through covalent inhibition that can explain the observed clinical effects and the dose–response characteristics of DMF treatment.

    • Jacob Lauwring Andersen
    • , Borbala Gesser
    •  & Poul Nissen

  • Article
    | Open Access

    Inteins can act as post-translational environmental sensors in vivo. Here the authors characterize two inteins present in the Mycobacterium smegmatis replicative helicase DnaB that display distinct splicing behaviors and are differentially sensitive to inhibition by biological stressors and propose that splicing inhibition could modulate DnaB levels to protect the cell against replication stress.

    • Danielle S. Kelley
    • , Christopher W. Lennon
    •  & Marlene Belfort

  • Article
    | Open Access

    Rhabdopeptides are synthesized by non-ribosomal peptide synthetases (NRPSs) and the multiple NRPS subunits interact through docking domains (DD). Here the authors provide insights into DD interaction patterns and present the structures of three N-terminal docking domains (NDD) and a NDD-CDD complex and derive a set of recognition rules for DD interactions.

    • Carolin Hacker
    • , Xiaofeng Cai
    •  & Jens Wöhnert

  • Article
    | Open Access

    Ischemic reperfusion or nutrient deprivation that produces reactive oxygen species can lead to a loss of muscle contractile function. Here the authors show that glutathionylation of the lysine methyltransferase SMYD2 contributes to degradation or disassembly of sarcomeres.

    • Dhanushka N. P. Munkanatta Godage
    • , Garrett C. VanHecke
    •  & Young-Hoon Ahn

  • Article
    | Open Access

    Enzymes of the six-transmembrane epithelial antigen of the prostate (STEAP) family reduce Fe3+ and Cu2+ ions to facilitate metal-ion uptake by mammalian cells. Here, authors employ single-particle cryo-EM to gain insights into the molecular principles of iron reduction by human STEAP4 .

    • Wout Oosterheert
    • , Laura S. van Bezouwen
    •  & Piet Gros

  • Article
    | Open Access

    It was previously suggested that formation of RNA secondary structure tends to bring the 5′ and 3′ ends of RNA into close proximity. Here the authors use experimental and computational approaches to show that mRNAs and lncRNAs have an intrinsic propensity to fold into structures in which the 5′ end and 3′ end are ≤7 nm apart irrespective of length.

    • Wan-Jung C. Lai
    • , Mohammad Kayedkhordeh
    •  & Dmitri N. Ermolenko

  • Article
    | Open Access

    The MILL (MHC-I-like located near the leukocyte receptor complex) family is a group of related nonclassical MHC-I molecules. Here the authors present the crystal structure of MILL2, which reveals an unusual interdomain flexibility, and show that MILL2 binds heparan sulfate on the surface of fibroblasts through a basic patch.

    • Mizuho Kajikawa
    • , Toyoyuki Ose
    •  & Katsumi Maenaka

  • Article
    | Open Access

    PWWP2A is a chromatin-binding transcriptional regulator that mediates mitosis-progression. Here, the authors provide evidence that PWWP2A directly interacts with H2A.Z nucleosomes, DNA and H3K36me3, binds to an MTA1-specific subcomplex of the NuRD complex (M1HR) and promotes changes to histone acetylation.

    • Stephanie Link
    • , Ramona M. M. Spitzer
    •  & Sandra B. Hake

  • Article
    | Open Access

    The type III secretion system effectors NleB and SseK are glycosyltransferases (GT) that specifically glycosylate arginine residues. Here the authors provide insights into their mechanism by combining X-ray crystallography, NMR, enzyme kinetics measurements, molecular dynamics simulations and in vivo experiments and show that SseK/NleB enzymes are retaining GTs.

    • Jun Bae Park
    • , Young Hun Kim
    •  & Hyun-Soo Cho

  • Article
    | Open Access

    Methane- and ammonia-oxidizing bacteria use the integral membrane, copper-dependent enzymes particulate methane monooxygenase (pMMO) and ammonia monooxygenase (AMO) to oxidize methane and ammonia. Here the authors structurally characterize the copper-binding protein PmoD, which contains an unusual CuA site and their genetic analyses strongly support a pMMO and AMO related function of PmoD.

    • Oriana S. Fisher
    • , Grace E. Kenney
    •  & Amy C. Rosenzweig

  • Article
    | Open Access

    Membrane bilayers are made up of a myriad of different lipids that affect membrane proteins, but identifying those specific lipid requirements remains a challenge. Here authors present an engineered thermal-shift screen which reveals specific lipid preferences of eukaryotic and prokaryotic membrane proteins.

    • Emmanuel Nji
    • , Yurie Chatzikyriakidou
    •  & David Drew

  • Article
    | Open Access

    Despite functional optimisation during evolution of parasitism, most members of a calcium dependent protein kinase (CDPK) family show genetic redundancy in Plasmodium. Here, the authors screen 294 genetic interactions among protein kinases in Plasmodium and show how some CDPKs functionally interact to control motility and host cell invasion.

    • Hanwei Fang
    • , Ana Rita Gomes
    •  & Mathieu Brochet

  • Article
    | Open Access

    Incorporation of mismatched nucleotides during DNA replication or repair can lead to mutagenesis. Here the authors reveal that DNA ligase can ligate NHEJ intermediates following incorporation of 8-oxodGTP or dGTP opposite T by DNA Polymerase mu (Pol mu) in vitro, which suggests that Pol mu could cause promutagenic mismatches during DSB repair.

    • Melike Çağlayan
    •  & Samuel H. Wilson

  • Article
    | Open Access

    Collagen proteins assemble into trimers from distinct monomers with high specificity, yet the molecular basis for this specificity remains unclear. Here the authors demonstrate the crucial role of conserved C-terminal domain cysteine residues and calcium in homotrimeric procollagen assembly.

    • Andrew S. DiChiara
    • , Rasia C. Li
    •  & Matthew D. Shoulders

  • Article
    | Open Access

    Cation/proton antiporters (CPAs) play a major role in maintaining living cells’ homeostasis and are divided in two main groups: CPA1 and CPA2. Here authors use a comprehensive evolutionary analysis of 6537 representative CPAs and reveal a sequence motif that determines central phenotypic characteristics.

    • Gal Masrati
    • , Manish Dwivedi
    •  & Nir Ben-Tal

  • Article
    | Open Access

    How G-quadruplexes (G4s) are resolved by helicases is still a matter of investigation. Here the authors provide mechanistic insight into G4s unwinding by presenting a crystal structure of resolved G4 DNA and the G4 binding domain of RecQ helicase from the bacterium Cronobacter sakazakii.

    • Andrew F. Voter
    • , Yupeng Qiu
    •  & James L. Keck

  • Article
    | Open Access

    Transient receptor potential mucolipin 1 (TRPML1) is a lysosomal channel which maintains the low pH and calcium levels for lysosomal function. Here authors use structural biology and electrophysiology to show how lipids bind and allosterically activate TRPML1.

    • Michael Fine
    • , Philip Schmiege
    •  & Xiaochun Li

  • Article
    | Open Access

    TRPV5 is a kidney specific transient receptor potential (TRP) channel with an important role in calcium reabsorption. Here the authors provide mechanistic insights into TRPV5 modulation by determining the phosphatidylinositol 4,5-bisphosphate and calmodulin bound TRPV5 cryo-EM structures.

    • Taylor E. T. Hughes
    • , Ruth A. Pumroy
    •  & Vera Y. Moiseenkova-Bell

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