Biochemistry

  • Article
    | Open Access

    In Parkinson’s disease (PD) the monomeric protein alpha-synuclein (aSyn) misfolds and aggregates into insoluble fibrils. Here the authors use NMR measurements and hydrogen–deuterium exchange mass spectrometry and find that the more solvent exposed the N-terminus of aSyn is, the more aggregation prone its conformation becomes, and further show how PD mutations and post translational modifications influence the extent of the N-terminus solvent exposure.

    • Amberley D. Stephens
    • , Maria Zacharopoulou
    • , Rani Moons
    • , Giuliana Fusco
    • , Neeleema Seetaloo
    • , Anass Chiki
    • , Philippa J. Woodhams
    • , Ioanna Mela
    • , Hilal A. Lashuel
    • , Jonathan J. Phillips
    • , Alfonso De Simone
    • , Frank Sobott
    •  & Gabriele S. Kaminski Schierle
  • Article
    | Open Access

    The Thoeris defense system is a recently discovered bacterial defense system that protects bacteria against phage infection and consists of the two genes thsA and thsB. Here, the authors present the crystal structures of Bacillus cereus ThsA and ThsB and show that ThsA is a NAD+ cleaving enzyme.

    • Donghyun Ka
    • , Hyejin Oh
    • , Eunyoung Park
    • , Jeong-Han Kim
    •  & Euiyoung Bae
  • Article
    | Open Access

    Mutation of the C-terminal extension of 5′-aminolevulinate synthase 2 (ALAS2) is the molecular cause for X-linked protoporphyria, but the underlying mechanism is unclear. Based on crystal structures and MD simulations of ALAS2, the authors here show how the C-terminal extension regulates ALAS2 activity.

    • Henry J. Bailey
    • , Gustavo A. Bezerra
    • , Jason R. Marcero
    • , Siladitya Padhi
    • , William R. Foster
    • , Elzbieta Rembeza
    • , Arijit Roy
    • , David F. Bishop
    • , Robert J. Desnick
    • , Gopalakrishnan Bulusu
    • , Harry A. Dailey Jr
    •  & Wyatt W. Yue
  • Article
    | Open Access

    FinO-domain proteins are bacterial RNA-binding proteins with a wide range of target specificities. Here, the authors employ UV CLIP-seq and show that minimal ProQ protein of Neisseria meningitidis binds to various small non-coding RNAs and mRNAs involved in virulence.

    • Saskia Bauriedl
    • , Milan Gerovac
    • , Nadja Heidrich
    • , Thorsten Bischler
    • , Lars Barquist
    • , Jörg Vogel
    •  & Christoph Schoen
  • Article
    | Open Access

    Tau plays an important role in tauopathies and undergoes liquid-liquid phase separation (LLPS). The authors show that disease-related P301L mutant and phosphomimic (S199E/S202E/T205E) tau enhance LLPS in vitro at physiological levels, and using specific antibodies, that tau LLPS leads to pathological conformations such as N-terminal exposure and oligomeric species.

    • Nicholas M. Kanaan
    • , Chelsey Hamel
    • , Tessa Grabinski
    •  & Benjamin Combs
  • Article
    | Open Access

    Age-associated metabolic changes include lipid accumulation. Here, the authors show that with replicative aging yeast accumulate lipid droplets which protect cells from cold stress and can be modulated through Biosynthesis of NAD+ 2 (BNA2).

    • Anthony O. Beas
    • , Patricia B. Gordon
    • , Clara L. Prentiss
    • , Carissa Perez Olsen
    • , Matthew A. Kukurugya
    • , Bryson D. Bennett
    • , Susan M. Parkhurst
    •  & Daniel E. Gottschling
  • Article
    | Open Access

    Previous study identified in vivo structured mRNA regions in Saccharomyces cerevisiae by dimethyl sulfate-sequencing. Here the authors use quantitative proteomics to identify protein interactors of 186 RNA folds in S. cerevisiae, providing functional links between RNA binding proteins and distinct mRNA fold.

    • Nuria Casas-Vila
    • , Sergi Sayols
    • , Lara Pérez-Martínez
    • , Marion Scheibe
    •  & Falk Butter
  • Article
    | Open Access

    Small molecule polyamines participate in diverse aspects of cell growth and differentiation and are known to regulate ion channel gating. Here authors reveal that cellular polyamines control nicotinic acetylcholine receptor (nAChR) biogenesis, and either catabolic degradation or inhibition of polyamine production augments nAChR assembly.

    • Madhurima Dhara
    • , Jose A. Matta
    • , Min Lei
    • , Daniel Knowland
    • , Hong Yu
    • , Shenyan Gu
    •  & David S. Bredt
  • Article
    | Open Access

    Riboswitches consist of an aptamer domain and expression platform, which senses a signal and regulates gene expression, respectively. Here the authors show that the expression platform of a SAM-I riboswitch from the Gram-negative bacteria can sense and bind uncharged an initiator Met tRNA to control the met operon.

    • Dong-Jie Tang
    • , Xinyu Du
    • , Qiang Shi
    • , Jian-Ling Zhang
    • , Yuan-Ping He
    • , Yan-Miao Chen
    • , Zhenhua Ming
    • , Dan Wang
    • , Wan-Ying Zhong
    • , Yu-Wei Liang
    • , Jin-Yang Liu
    • , Jian-Ming Huang
    • , Yun-Shi Zhong
    • , Shi-Qi An
    • , Hongzhou Gu
    •  & Ji-Liang Tang
  • Article
    | Open Access

    Study of human heart failure is limited by access to human tissue. Here, the authors apply multi-omic screening in human ischaemic and dilated myocardial tissue and matched controls to determine molecular changes common and unique to each aetiology and to reveal differences between male and female hearts.

    • Mengbo Li
    • , Benjamin L. Parker
    • , Evangeline Pearson
    • , Benjamin Hunter
    • , Jacob Cao
    • , Yen Chin Koay
    • , Oneka Guneratne
    • , David E. James
    • , Jean Yang
    • , Sean Lal
    •  & John F. O’Sullivan
  • Article
    | Open Access

    Immunopeptidomics allows identifying the cellular repertoire of MHC-bound peptides, but quantifying them remains challenging. Here, the authors present a method to efficiently generate internal peptide MHC standards and calibration curves, facilitating relative and absolute quantitative immunopeptidomics.

    • Lauren E. Stopfer
    • , Joshua M. Mesfin
    • , Brian A. Joughin
    • , Douglas A. Lauffenburger
    •  & Forest M. White
  • Article
    | Open Access

    The bacterial effector MavC can ubiquitinate the host E2 enzyme UBE2N to dampen the host immune response. Here, the authors provide mechanistic insight into this non-canonical ubiquitination machinery and reveal the structural basis for the functional differences between MavC and its close homolog MvcA.

    • Yong Wang
    • , Qi Zhan
    • , Xinlu Wang
    • , Peipei Li
    • , Songqing Liu
    • , Guangxia Gao
    •  & Pu Gao
  • Article
    | Open Access

    3′ end of microRNAs binds to the PAZ domain of Argonaute (AGO) proteins. Here the authors show that terminal nucleotidyltransferases TUT4/7 and exonuclease DIS3L2 induce tailing and decay of 3’ end exposed-microRNAs in AGO PAZ mutant expressing- or cancer cells.

    • Acong Yang
    • , Tie-Juan Shao
    • , Xavier Bofill-De Ros
    • , Chuanjiang Lian
    • , Patricia Villanueva
    • , Lisheng Dai
    •  & Shuo Gu
  • Article
    | Open Access

    Many metalloenzymes are highly specific for their cognate metal ion but the molecular principles underlying this specificity often remain unclear. Here, the authors characterize the structural and biochemical basis for the different metal specificity of two evolutionarily related superoxide dismutases.

    • Anna Barwinska-Sendra
    • , Yuritzi M. Garcia
    • , Kacper M. Sendra
    • , Arnaud Baslé
    • , Eilidh S. Mackenzie
    • , Emma Tarrant
    • , Patrick Card
    • , Leandro C. Tabares
    • , Cédric Bicep
    • , Sun Un
    • , Thomas E. Kehl-Fie
    •  & Kevin J. Waldron
  • Article
    | Open Access

    The anti-CRISPR protein IF9 (AcrIF9) specifically inhibits the type I-F CRISPR adaptive immune system. Here, the authors present the cryo-EM structure of AcrIF9 in complex with the type I-F CRISPR RNA-guided surveillance complex (Csy) and a dsDNA bound Csy-AcrIF9 structure, and find that AcrIF9 binding to the Csy complex triggers non-sequence specific dsDNA binding to Csy-AcrIF9, which might sequester the complex from its target DNA.

    • Marscha Hirschi
    • , Wang-Ting Lu
    • , Andrew Santiago-Frangos
    • , Royce Wilkinson
    • , Sarah M. Golden
    • , Alan R. Davidson
    • , Gabriel C. Lander
    •  & Blake Wiedenheft
  • Article
    | Open Access

    Although Tc toxins are a major class of bacterial toxin translocation systems, little is known about their receptor binding. Here, the authors identify heparins/heparan sulfates and Lewis antigens as receptors for different Tc toxins, determine cryo-EM structures of three toxin-glycan complexes and propose a two-step cell adhesion mechanism for Tc toxins.

    • Daniel Roderer
    • , Felix Bröcker
    • , Oleg Sitsel
    • , Paulina Kaplonek
    • , Franziska Leidreiter
    • , Peter H. Seeberger
    •  & Stefan Raunser
  • Article
    | Open Access

    DmpR is a bacterial enhancer binding protein from the AAA+ family of ATPases that binds aromatic compounds and controls the transcription of genes involved in the degradation of toxic pollutants. Here, the authors present the crystal structure of phenol-bound DmpR, which forms a tetramer and discuss its signal transduction mechanism.

    • Kwang-Hyun Park
    • , Sungchul Kim
    • , Su-Jin Lee
    • , Jee-Eun Cho
    • , Vinod Vikas Patil
    • , Arti Baban Dumbrepatil
    • , Hyung-Nam Song
    • , Woo-Chan Ahn
    • , Chirlmin Joo
    • , Seung-Goo Lee
    • , Victoria Shingler
    •  & Eui-Jeon Woo
  • Article
    | Open Access

    α-Syn in CSF is a biomarker of neurodegenerative diseases; however, the detection of clinically relevant species is difficult. Here, the authors create a nanobody biosensor that reveals the presence of α-Syn in cells, which allow the detection of transmittable forms of α-Syn present in human CSF.

    • Christoph Gerdes
    • , Natalia Waal
    • , Thomas Offner
    • , Eugenio F. Fornasiero
    • , Nora Wender
    • , Hannes Verbarg
    • , Ivan Manzini
    • , Claudia Trenkwalder
    • , Brit Mollenhauer
    • , Timo Strohäker
    • , Markus Zweckstetter
    • , Stefan Becker
    • , Silvio O. Rizzoli
    • , Fitnat Buket Basmanav
    •  & Felipe Opazo
  • Article
    | Open Access

    WIPI proteins are mammalian PROPPIN family phosphoinositide effectors that recognize a WIPI-interacting-region (WIR)-motif to recruit other regulators during autophagosome formation. Here, the authors combine structural and functional studies and present the crystal structure of human WIPI3 with a bound ATG2A WIR-peptide and observe that the WIR-motif binds to three sites in blades 1-3 of WIPI3 and mutating these binding sites impairs the ATG2A-mediated autophagic process.

    • Jinqi Ren
    • , Ruobing Liang
    • , Wenjuan Wang
    • , Dachuan Zhang
    • , Li Yu
    •  & Wei Feng
  • Article
    | Open Access

    Self-sufficient cytochrome P450 monooxygenases, which contain all redox partners in a single polypeptide chain, are of interest for biotechnological applications. Here, the authors present the crystal structure of full-length Thermobispora bispora CYP116B46 and discuss the potential electron transfer pathway.

    • Lilan Zhang
    • , Zhenzhen Xie
    • , Ziwei Liu
    • , Shuyu Zhou
    • , Lixin Ma
    • , Weidong Liu
    • , Jian-Wen Huang
    • , Tzu-Ping Ko
    • , Xiuqin Li
    • , Yuechan Hu
    • , Jian Min
    • , Xuejing Yu
    • , Rey-Ting Guo
    •  & Chun-Chi Chen
  • Article
    | Open Access

    ESCRT-III proteins assemble into ubiquitous membrane-remodeling polymers during many cellular processes. Here, the authors use cryo-ET, cryo-EM and mathematical modeling to reveal how the shape of the helical membrane tube arises from the assembly of two distinct bundles of helical filaments.

    • Joachim Moser von Filseck
    • , Luca Barberi
    • , Nathaniel Talledge
    • , Isabel E. Johnson
    • , Adam Frost
    • , Martin Lenz
    •  & Aurélien Roux
  • Article
    | Open Access

    RNA G-quadruplexes (RG4s) have been functionally linked to cancer gene expression. Here, Herviou, Le Bras et al. have identified the protein machinery modulating RG4s and reveal the role and mechanism of hnRNP H/F and DHX36 in RG4-mediated translational regulation affecting cancer treatment in glioblastoma.

    • Pauline Herviou
    • , Morgane Le Bras
    • , Leïla Dumas
    • , Corinne Hieblot
    • , Julia Gilhodes
    • , Gianluca Cioci
    • , Jean-Philippe Hugnot
    • , Alfred Ameadan
    • , François Guillonneau
    • , Erik Dassi
    • , Anne Cammas
    •  & Stefania Millevoi
  • Article
    | Open Access

    Glycosylation plays a key role in shielding of immunogenic epitopes on viral spike (S) proteins. Here Watanabe et al. report that glycans of coronavirus SARS and MERS S proteins are heterogeneously distributed and do not form an efficacious high-density global shield which would ensure efficient immune evasion.

    • Yasunori Watanabe
    • , Zachary T. Berndsen
    • , Jayna Raghwani
    • , Gemma E. Seabright
    • , Joel D. Allen
    • , Oliver G. Pybus
    • , Jason S. McLellan
    • , Ian A. Wilson
    • , Thomas A. Bowden
    • , Andrew B. Ward
    •  & Max Crispin
  • Article
    | Open Access

    The Legionella pneumophila Dot/Icm type IVB secretion system (T4BSS) translocates effector proteins into host cells, and the recognition of these effectors is mediated by the Dot/Icm type IV coupling protein (T4CP) complex. Here, the authors present the crystal structure of a four-subunit containing T4CP subcomplex bound to the effector protein VpdB, and identify a FxxxLxxxK binding motif that is present in a subset of the effectors and which is recognized by the T4CP adaptor subunit LvgA.

    • Hyunmin Kim
    • , Tomoko Kubori
    • , Kohei Yamazaki
    • , Mi-Jeong Kwak
    • , Suk-Youl Park
    • , Hiroki Nagai
    • , Joseph P. Vogel
    •  & Byung-Ha Oh
  • Article
    | Open Access

    The E46K α-synuclein mutation causes familial Parkinson’s disease. Here, the authors present the cryo-EM structure of N-terminally acetylated E46K α-synuclein fibrils and find that it is distinct from other known α-synuclein fibril structures.

    • Kun Zhao
    • , Yaowang Li
    • , Zhenying Liu
    • , Houfang Long
    • , Chunyu Zhao
    • , Feng Luo
    • , Yunpeng Sun
    • , Youqi Tao
    • , Xiao-dong Su
    • , Dan Li
    • , Xueming Li
    •  & Cong Liu
  • Article
    | Open Access

    Enzymes from organisms inhabiting cold environments (psychrophiles) have adapted to catalyzing chemical reactions at near freezing temperatures. Here – using molecular dynamics simulations – the authors analyze cold adaptation of psychrophilic α-amylase and provide the structural basis for its low anomalous temperature optimum: the increased mobility of a surface loop involved in substrate interaction.

    • Jaka Sočan
    • , Miha Purg
    •  & Johan Åqvist
  • Article
    | Open Access

    The bromodomain containing protein BRD9 has been reported to regulate chromatin remodeling and transcription. Here the authors reveal a role for BRD9 in homologous recombination by facilitating RAD51–RAD54 interaction.

    • Qin Zhou
    • , Jinzhou Huang
    • , Chao Zhang
    • , Fei Zhao
    • , Wootae Kim
    • , Xinyi Tu
    • , Yong Zhang
    • , Somaira Nowsheen
    • , Qian Zhu
    • , Min Deng
    • , Yuping Chen
    • , Bo Qin
    • , Kuntian Luo
    • , Baohua Liu
    • , Zhenkun Lou
    • , Robert W. Mutter
    •  & Jian Yuan
  • Article
    | Open Access

    F1Fo ATP synthase consists of two coupled rotary molecular motors: the soluble ATPase F1 and the transmembrane Fo. Here, the authors present cryo-EM structures of E. coli ATP synthase in four discrete rotational sub-states at 3.1-3.4 Å resolution and observe a rotary sub-step of the Fo motor cring that reveals the mechanism of elastic coupling between the two rotary motors, which is essential for effective ATP synthesis.

    • Meghna Sobti
    • , James L. Walshe
    • , Di Wu
    • , Robert Ishmukhametov
    • , Yi C. Zeng
    • , Carol V. Robinson
    • , Richard M. Berry
    •  & Alastair G. Stewart
  • Article
    | Open Access

    The number of usable light-responsive enzymes is limited, despite the potential biotechnological applications. Here, the authors report a flavoprotein monooxygenase which is controllable by blue light illumination, and propose a mechanism involving protein-mediated radical photoreduction of FAD via a semiquinone intermediate.

    • Simon Ernst
    • , Stefano Rovida
    • , Andrea Mattevi
    • , Susanne Fetzner
    •  & Steffen L. Drees
  • Article
    | Open Access

    During translocation by viral RNA-dependent RNA polymerases (RdRP), the template-product RNA duplex moves in an asymmetric manner. Here the authors describe several crystal structures of RdRP translocations intermediates that, along with enzymological data, provide a comprehensive view of RdRP translocation.

    • Meihua Wang
    • , Rui Li
    • , Bo Shu
    • , Xuping Jing
    • , Han-Qing Ye
    •  & Peng Gong
  • Article
    | Open Access

    There is a need to further improve the automation of cryo-EM sample preparation to make it more easily accessible for non-specialists, reduce sample waste and increase reproducibility. Here, the authors present VitroJet, a single device, where sub-nl volumes of samples are deposited by pin printing thus eliminating the need for sample blotting, which is followed by jet vitrification, and they show that high-resolution structures can be obtained using four standard proteins.

    • Raimond B. G. Ravelli
    • , Frank J. T. Nijpels
    • , Rene J. M. Henderikx
    • , Giulia Weissenberger
    • , Sanne Thewessem
    • , Abril Gijsbers
    • , Bart W. A. M. M. Beulen
    • , Carmen López-Iglesias
    •  & Peter J. Peters
  • Article
    | Open Access

    Gene isoforms result from variable transcription start sites (TSSs) and polyadenylation sites (PASs) at the end of transcripts. Here, the authors perform transcript isoform sequencing and find widespread promoter- proximal transcriptional termination in Arabidopsis, suggesting this may represent a checkpoint that regulates plant gene expression.

    • Quentin Angelo Thomas
    • , Ryan Ard
    • , Jinghan Liu
    • , Bingnan Li
    • , Jingwen Wang
    • , Vicent Pelechano
    •  & Sebastian Marquardt
  • Article
    | Open Access

    Androgen receptor (AR) signalling regulates cellular metabolism in prostate cancer. Here, the authors perform a proteomics and metabolomics characterisation of prostate cancer cells adapted to long-term resistance to AR inhibition and show rewiring of glucose and lipid metabolism, and further identify a signature associated with resistance to AR inhibition.

    • Arnaud Blomme
    • , Catriona A. Ford
    • , Ernest Mui
    • , Rachana Patel
    • , Chara Ntala
    • , Lauren E. Jamieson
    • , Mélanie Planque
    • , Grace H. McGregor
    • , Paul Peixoto
    • , Eric Hervouet
    • , Colin Nixon
    • , Mark Salji
    • , Luke Gaughan
    • , Elke Markert
    • , Peter Repiscak
    • , David Sumpton
    • , Giovanny Rodriguez Blanco
    • , Sergio Lilla
    • , Jurre J. Kamphorst
    • , Duncan Graham
    • , Karen Faulds
    • , Gillian M. MacKay
    • , Sarah-Maria Fendt
    • , Sara Zanivan
    •  & Hing Y. Leung
  • Article
    | Open Access

    METTL2 methyltransferase is responsible for 3-methylcytosine modification of arginine tRNAs in mammals. Here the authors show that DALR anticodon binding domain containing 3 (DALRD3) forms a complex with METTL2 to recognize specific arginine tRNAs and find DALRD3 mutations in patients with developmental delay and early-onset epileptic encephalopathy.

    • Jenna M. Lentini
    • , Hessa S. Alsaif
    • , Eissa Faqeih
    • , Fowzan S. Alkuraya
    •  & Dragony Fu
  • Article
    | Open Access

    Sterol O-acyltransferase 1 (SOAT1, also named ACAT1) is an endoplasmic reticulum resident enzyme which catalyzes the esterification of cholesterol to generate cholesteryl esters. Here, authors report cryo-EM structures of human SOAT1 which reveal the binding site of the competitive inhibitor CI-976.

    • Chengcheng Guan
    • , Yange Niu
    • , Si-Cong Chen
    • , Yunlu Kang
    • , Jing-Xiang Wu
    • , Koji Nishi
    • , Catherine C. Y. Chang
    • , Ta-Yuan Chang
    • , Tuoping Luo
    •  & Lei Chen
  • Article
    | Open Access

    One of the major photosynthetic light-harvesting complexes (LHCs) are fucoxanthin chlorophyll a/c-binding proteins (FCPs), which are present in diatoms, a major group of algae. Here, the authors present the cryo-EM structure of the photosystem I-FCP (PSI-FCPI) supercomplex isolated from the marine centric diatom Chaetoceros gracilis that contains 16 FCPI subunits surrounding the PSI core and discuss possible excitation energy transfer pathways.

    • Ryo Nagao
    • , Koji Kato
    • , Kentaro Ifuku
    • , Takehiro Suzuki
    • , Minoru Kumazawa
    • , Ikuo Uchiyama
    • , Yasuhiro Kashino
    • , Naoshi Dohmae
    • , Seiji Akimoto
    • , Jian-Ren Shen
    • , Naoyuki Miyazaki
    •  & Fusamichi Akita
  • Article
    | Open Access

    DNA polymerase epsilon (Pol ε) synthesizes half of the genome in every cell cycle. Here the authors uncover a dual role of a unique domain within the Pol ε catalytic core in replisome assembly and DNA synthesis and the impact of this domain on genome stability.

    • Xiangzhou Meng
    • , Lei Wei
    • , Sujan Devbhandari
    • , Tuo Zhang
    • , Jenny Xiang
    • , Dirk Remus
    •  & Xiaolan Zhao
  • Article
    | Open Access

    The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation is located near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here the authors assessed M305L actin in vivo, in vitro, and in silico to characterize emergent pathological properties and define the mechanistic basis of disease.

    • Meera C. Viswanathan
    • , William Schmidt
    • , Peter Franz
    • , Michael J. Rynkiewicz
    • , Christopher S. Newhard
    • , Aditi Madan
    • , William Lehman
    • , Douglas M. Swank
    • , Matthias Preller
    •  & Anthony Cammarato
  • Article
    | Open Access

    The essential role of ORAI1 channels in receptor-evoked Ca2+ signaling is well understood, but the roles of ORAI2 and ORAI3 remained obscure. Here authors show that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca2+ signals, reflecting their enhanced basal STIM1-binding and heightened Ca2+-dependent inactivation.

    • Ryan E. Yoast
    • , Scott M. Emrich
    • , Xuexin Zhang
    • , Ping Xin
    • , Martin T. Johnson
    • , Adam J. Fike
    • , Vonn Walter
    • , Nadine Hempel
    • , David I. Yule
    • , James Sneyd
    • , Donald L. Gill
    •  & Mohamed Trebak
  • Article
    | Open Access

    Protein-protein interactions are fundamental to the regulation of protein activity and cellular phyisology. Here the authors present Split Intein-Mediated Protein Ligation, which uses bait and prey proteins fused to intein fragments to generate single intact proteins upon interaction.

    • Zhong Yao
    • , Farzaneh Aboualizadeh
    • , Jason Kroll
    • , Indira Akula
    • , Jamie Snider
    • , Anna Lyakisheva
    • , Priscilla Tang
    • , Max Kotlyar
    • , Igor Jurisica
    • , Mike Boxem
    •  & Igor Stagljar
  • Article
    | Open Access

    Proton-linked monocarboxylate transporters (MCTs) facilitate monocarboxylate efflux in glycolytically active cells and regulate transport down in glycolytically inactive cells. Here authors show a steep dependence of human MCT2 activity on substrate concentration and show the structural basis of cooperative transport.

    • Bo Zhang
    • , Qiuheng Jin
    • , Lizhen Xu
    • , Ningning Li
    • , Ying Meng
    • , Shenghai Chang
    • , Xiang Zheng
    • , Jiangqin Wang
    • , Yuan Chen
    • , Dante Neculai
    • , Ning Gao
    • , Xiaokang Zhang
    • , Fan Yang
    • , Jiangtao Guo
    •  & Sheng Ye
  • Article
    | Open Access

    In fission yeast, several lncRNAs act in cis to regulate expression of adjacent genes. Here, the authors show that the conserved Pir2ARS2 protein is targeted, along with splicing factors, to cryptic introns in lncRNAs and recruits effectors, including RNAi machinery, for gene repression.

    • Gobi Thillainadesan
    • , Hua Xiao
    • , Sahana Holla
    • , Jothy Dhakshnamoorthy
    • , Lisa M. Miller Jenkins
    • , David Wheeler
    •  & Shiv I. S. Grewal
  • Article
    | Open Access

    The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.

    • Natalie C. Bamford
    • , François Le Mauff
    • , Jaime C. Van Loon
    • , Hanna Ostapska
    • , Brendan D. Snarr
    • , Yongzhen Zhang
    • , Elena N. Kitova
    • , John S. Klassen
    • , Jeroen D. C. Codée
    • , Donald C. Sheppard
    •  & P. Lynne Howell
  • Article
    | Open Access

    Protein arginine methyltransferases (PRMTs) are increasingly recognized as potential therapeutic targets but PRMT7 remains an understudied member of this enzyme family. Here, the authors develop a chemical probe for PRMT7 and apply it to elucidate the role of PRMT7 in the cellular stress response.

    • Magdalena M. Szewczyk
    • , Yoshinori Ishikawa
    • , Shawna Organ
    • , Nozomu Sakai
    • , Fengling Li
    • , Levon Halabelian
    • , Suzanne Ackloo
    • , Amber L. Couzens
    • , Mohammad Eram
    • , David Dilworth
    • , Hideto Fukushi
    • , Rachel Harding
    • , Carlo C. dela Seña
    • , Tsukasa Sugo
    • , Kozo Hayashi
    • , David McLeod
    • , Carlos Zepeda
    • , Ahmed Aman
    • , Maria Sánchez-Osuna
    • , Eric Bonneil
    • , Shinji Takagi
    • , Rima Al-Awar
    • , Mike Tyers
    • , Stephane Richard
    • , Masayuki Takizawa
    • , Anne-Claude Gingras
    • , Cheryl H. Arrowsmith
    • , Masoud Vedadi
    • , Peter J. Brown
    • , Hiroshi Nara
    •  & Dalia Barsyte-Lovejoy
  • Article
    | Open Access

    Trefoil factors (TFFs) protect the mucosa and have various reported binding activities, but whether they share a common interaction mechanism has remained unclear. Here, the authors provide structural and biochemical evidence that all three human TFFs are divalent lectins that recognise the same disaccharide.

    • Michael A. Järvå
    • , James P. Lingford
    • , Alan John
    • , Niccolay Madiedo Soler
    • , Nichollas E. Scott
    •  & Ethan D. Goddard-Borger
  • Article
    | Open Access

    The Legionella pneumophila effector MavC inhibits the human ubiquitin-conjugating enzyme Ube2N. Here, the authors combine NMR, X-ray crystallography and biochemical assays and show that MavC catalyses the intramolecular transglutaminase reaction between the Ube2N and Ub subunits of the Ube2NUb conjugate and present the substrate- and product-bound MavC crystal structures.

    • Kedar Puvar
    • , Shalini Iyer
    • , Jiaqi Fu
    • , Sebastian Kenny
    • , Kristos I. Negrón Terón
    • , Zhao-Qing Luo
    • , Peter S. Brzovic
    • , Rachel E. Klevit
    •  & Chittaranjan Das
  • Article
    | Open Access

    Many pathogens manipulate ubiquitin-mediated signaling to evade host cell defense. Here, the authors characterize the structure and enzymatic activity of a deubiquitylase domain from the causative pathogen of scrub typhus, providing evidence for a distinct mechanism of ubiquitin chain selectivity.

    • Jason M. Berk
    • , Christopher Lim
    • , Judith A. Ronau
    • , Apala Chaudhuri
    • , Hongli Chen
    • , John F. Beckmann
    • , J. Patrick Loria
    • , Yong Xiong
    •  & Mark Hochstrasser
  • Article
    | Open Access

    Recombinant T-cells receptors can redirect naïve T cells but often have low or uneven expression. Here, the authors model mutations in TCR constant domains to increase T cell receptor expression, assembly, and stability and generate bispecific molecules.

    • Karen Froning
    • , Jack Maguire
    • , Arlene Sereno
    • , Flora Huang
    • , Shawn Chang
    • , Kenneth Weichert
    • , Anton J. Frommelt
    • , Jessica Dong
    • , Xiufeng Wu
    • , Heather Austin
    • , Elaine M. Conner
    • , Jonathan R. Fitchett
    • , Aik Roy Heng
    • , Deepa Balasubramaniam
    • , Mark T. Hilgers
    • , Brian Kuhlman
    •  & Stephen J. Demarest
  • Article
    | Open Access

    Auxin-mediated recruitment of AUX/IAAs by the F-box protein TIR1 prompts rapid AUX/IAA ubiquitylation and degradation. By resolving auxin receptor topology, the authors show that intrinsically disordered regions near the degrons of two Aux/IAA proteins reinforce complex assembly and position Aux/IAAs for ubiquitylation.

    • Michael Niemeyer
    • , Elena Moreno Castillo
    • , Christian H. Ihling
    • , Claudio Iacobucci
    • , Verona Wilde
    • , Antje Hellmuth
    • , Wolfgang Hoehenwarter
    • , Sophia L. Samodelov
    • , Matias D. Zurbriggen
    • , Panagiotis L. Kastritis
    • , Andrea Sinz
    •  & Luz Irina A. Calderón Villalobos
  • Article
    | Open Access

    Macrophages undergo a Warburg-like switch from oxidative phosphorylation to glycolysis in response to inflammatory stimulus. Here the authors show that fungal melanin can trigger this switch in human macrophages by sequestering calcium in the phagosome and enabling protection against Aspergillus fumigatus infection.

    • Samuel M. Gonçalves
    • , Cláudio Duarte-Oliveira
    • , Cláudia F. Campos
    • , Vishukumar Aimanianda
    • , Rob ter Horst
    • , Luis Leite
    • , Toine Mercier
    • , Paulo Pereira
    • , Miguel Fernández-García
    • , Daniela Antunes
    • , Cláudia S. Rodrigues
    • , Catarina Barbosa-Matos
    • , Joana Gaifem
    • , Inês Mesquita
    • , António Marques
    • , Nuno S. Osório
    • , Egídio Torrado
    • , Fernando Rodrigues
    • , Sandra Costa
    • , Leo AB. Joosten
    • , Katrien Lagrou
    • , Johan Maertens
    • , João F. Lacerda
    • , António Campos Jr.
    • , Gordon D. Brown
    • , Axel A. Brakhage
    • , Coral Barbas
    • , Ricardo Silvestre
    • , Frank L. van de Veerdonk
    • , Georgios Chamilos
    • , Mihai G. Netea
    • , Jean-Paul Latgé
    • , Cristina Cunha
    •  & Agostinho Carvalho