Structural biology

  • 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

    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

    Cryo-electron microscopy is widely employed in structural biology and uses phase contrast imaging. Here, the authors employ electron ptychography, a quantitative phase retrieval method for high-contrast, low-dose phase imaging of cryo-state rotavirus and immature HIV-1 virus-like particles, and show that electron ptychography is more efficient for phase recovery than conventional phase contrast imaging.

    • Liqi Zhou
    • , Jingdong Song
    • , Judy S. Kim
    • , Xudong Pei
    • , Chen Huang
    • , Mark Boyce
    • , Luiza Mendonça
    • , Daniel Clare
    • , Alistair Siebert
    • , Christopher S. Allen
    • , Emanuela Liberti
    • , David Stuart
    • , Xiaoqing Pan
    • , Peter D. Nellist
    • , Peijun Zhang
    • , Angus I. Kirkland
    •  & Peng Wang
  • 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

    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

    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

    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

    ESCRT-III complexes assemble in vivo inside membrane structures with a negative Gaussian curvature, but how membrane shape influences ESCRT-III polymerization remains unclear. Here authors use structural and biophysical methods to show how human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation.

    • Aurélie Bertin
    • , Nicola de Franceschi
    • , Eugenio de la Mora
    • , Sourav Maiti
    • , Maryam Alqabandi
    • , Nolwen Miguet
    • , Aurélie di Cicco
    • , Wouter H. Roos
    • , Stéphanie Mangenot
    • , Winfried Weissenhorn
    •  & Patricia Bassereau
  • 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

    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

    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

    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

    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

    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

    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

    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

    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

    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

    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

    Constitutive Btk signaling drives several B-cell cancers. Here the authors demonstrate key allosteric intramolecular interactions between the SH2 domain and the kinase domain of Btk, and propose an alternative approach for inhibition of both wild-type and tyrosine kinase inhibitor-resistant Btk.

    • Daniel P. Duarte
    • , Allan J. Lamontanara
    • , Giuseppina La Sala
    • , Sukyo Jeong
    • , Yoo-Kyoung Sohn
    • , Alejandro Panjkovich
    • , Sandrine Georgeon
    • , Tim Kükenshöner
    • , Maria J. Marcaida
    • , Florence Pojer
    • , Marco De Vivo
    • , Dmitri Svergun
    • , Hak-Sung Kim
    • , Matteo Dal Peraro
    •  & Oliver Hantschel
  • Article
    | Open Access

    The DNA methyltransferase DNMT3A plays an important role in establishing the DNA methylation patterns during development and deregulation of DNMT3A is associated with hematological cancers, with the R882H mutation the most frequently occurring DNMT3A missense mutation in acute myeloid leukemia. Here, the authors present the crystal structures of wild-type and R882H DNMT3A in complex with different DNA substrates and explain why the R882H mutation compromises the enzymatic activity of DNMT3A.

    • Hiwot Anteneh
    • , Jian Fang
    •  & Jikui Song
  • Article
    | Open Access

    ABCG2 is a human ABC transporter that actively extrudes a wide variety of compounds from cells but the mechanisms of multidrug transport remain obscure. Here authors present cryo-EM structures of ABCG2 in the apo state, and bound to the three structurally distinct chemotherapeutics and demonstrate how these molecules open the closed conformation of the transporter.

    • Benjamin J. Orlando
    •  & Maofu Liao
  • Article
    | Open Access

    HIV-1 envelope glycoprotein (Env) mediates the fusion of viral and target cell membranes and is a major target for HIV vaccine development. Here, the authors determine the NMR structure of a bicelle incorporated Env segment comprising the transmembrane domain (TMD) and a portion of the cytoplasmic tail (CT), and show that the CT folds into membrane attached amphipathic helices that wrap around the TMD thereby forming a support baseplate for the rest of Env, and they also provide insights into the dynamic coupling across the TMD between the ectodomain and CT.

    • Alessandro Piai
    • , Qingshan Fu
    • , Yongfei Cai
    • , Fadi Ghantous
    • , Tianshu Xiao
    • , Md Munan Shaik
    • , Hanqin Peng
    • , Sophia Rits-Volloch
    • , Wen Chen
    • , Michael S. Seaman
    • , Bing Chen
    •  & James J. Chou
  • Article
    | Open Access

    Plant metacaspases mediate immune response following activation by Ca2+. Here, via crystallography and functional analyses, the authors show that a linker domain in Arabidopsis Metacaspase 4 blocks substrate access to the active site but is cleaved multiple times in the presence of Ca2+ to allow enzyme activation.

    • Ping Zhu
    • , Xiao-Hong Yu
    • , Cheng Wang
    • , Qingfang Zhang
    • , Wu Liu
    • , Sean McSweeney
    • , John Shanklin
    • , Eric Lam
    •  & Qun Liu
  • Article
    | Open Access

    WUSCHEL is a homeodomain transcription factor that is essential for stem cell maintenance in the plant shoot apical meristem. Here, via structural and biochemical approaches, Sloan et al. show that strong WUSCHEL binding to preferential target motifs can be attributed to dimer formation that stabilizes DNA binding.

    • Jeremy Sloan
    • , Jana P. Hakenjos
    • , Michael Gebert
    • , Olga Ermakova
    • , Andrea Gumiero
    • , Gunter Stier
    • , Klemens Wild
    • , Irmgard Sinning
    •  & Jan U. Lohmann
  • Article
    | Open Access

    Type IV pili are flexible filaments on the surface of bacteria, consisting of a helical assembly of pilin proteins. Here, Neuhaus et al. show that the bacterium Thermus thermophilus produces two forms of type IV pilus, differing in structure, protein composition, and function.

    • Alexander Neuhaus
    • , Muniyandi Selvaraj
    • , Ralf Salzer
    • , Julian D. Langer
    • , Kerstin Kruse
    • , Lennart Kirchner
    • , Kelly Sanders
    • , Bertram Daum
    • , Beate Averhoff
    •  & Vicki A. M. Gold
  • Article
    | Open Access

    Signal transmission and regulation of G-protein-coupled receptors (GPCRs) by ligands occurs via modulation of complex conformational equilibria. Here authors quantify these equilibria and their dynamics in the β1-adrenergic receptor in its apo form and seven ligand complexes using NMR.

    • Anne Grahl
    • , Layara Akemi Abiko
    • , Shin Isogai
    • , Timothy Sharpe
    •  & Stephan Grzesiek
  • Article
    | Open Access

    The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs) promotes excitatory synapse formation. Here authors report the high resolution cryo-EM structure of the TEN2-LPHN3 complex, describe the trimeric TEN2-LPHN3-FLRT3 complex and show how alternative-splicing regulates the TEN2-LPHN3 interaction.

    • Jingxian Li
    • , Yuan Xie
    • , Shaleeka Cornelius
    • , Xian Jiang
    • , Richard Sando
    • , Szymon P. Kordon
    • , Man Pan
    • , Katherine Leon
    • , Thomas C. Südhof
    • , Minglei Zhao
    •  & Demet Araç
  • Article
    | Open Access

    Dpr (Defective proboscis extension response) and DIP (Dpr Interacting Proteins) are immunoglobulin-like cell-cell adhesion proteins that form highly specific pairwise interactions, which control synaptic connectivity during Drosophila development. Here, the authors combine a computational approach with binding affinity measurements and find that DIP/Dpr binding specificity is controlled by negative constraints that interfere with non-cognate binding.

    • Alina P. Sergeeva
    • , Phinikoula S. Katsamba
    • , Filip Cosmanescu
    • , Joshua J. Brewer
    • , Goran Ahlsen
    • , Seetha Mannepalli
    • , Lawrence Shapiro
    •  & Barry Honig
  • Article
    | Open Access

    Enzymatic inactivation of gibberellins and auxin, via GA2ox3 and DAO respectively, contributes to hormone homeostasis in plants. Here Takehara et al. show that both enzymes multimerize in a substrate-concentration-dependent manner, and that this multimerization leads to increased enzyme activity.

    • Sayaka Takehara
    • , Shun Sakuraba
    • , Bunzo Mikami
    • , Hideki Yoshida
    • , Hisako Yoshimura
    • , Aya Itoh
    • , Masaki Endo
    • , Nobuhisa Watanabe
    • , Takayuki Nagae
    • , Makoto Matsuoka
    •  & Miyako Ueguchi-Tanaka
  • Article
    | Open Access

    The Na+-pumping KR2 rhodopsin from Krokinobacter eikastus is a light-driven non-proton cation pump whose mechanism of pumping remains to be understood. Here authors solved crystal structures of the O-intermediate state of the pentameric form of KR2 and its D116N and H30A mutants, which sheds light on the mechanism of non-proton cation light-driven pumping.

    • Kirill Kovalev
    • , Roman Astashkin
    • , Ivan Gushchin
    • , Philipp Orekhov
    • , Dmytro Volkov
    • , Egor Zinovev
    • , Egor Marin
    • , Maksim Rulev
    • , Alexey Alekseev
    • , Antoine Royant
    • , Philippe Carpentier
    • , Svetlana Vaganova
    • , Dmitrii Zabelskii
    • , Christian Baeken
    • , Ilya Sergeev
    • , Taras Balandin
    • , Gleb Bourenkov
    • , Xavier Carpena
    • , Roeland Boer
    • , Nina Maliar
    • , Valentin Borshchevskiy
    • , Georg Büldt
    • , Ernst Bamberg
    •  & Valentin Gordeliy
  • Article
    | Open Access

    The chaperone SurA is involved in outer membrane protein (OMP) biogenesis in Gram-negative bacteria, but its mechanism of action is not fully understood. Combining mass spectrometric, biophysical and computational approaches, the authors here show how the conformational dynamics of SurA facilitate OMP binding.

    • Antonio N. Calabrese
    • , Bob Schiffrin
    • , Matthew Watson
    • , Theodoros K. Karamanos
    • , Martin Walko
    • , Julia R. Humes
    • , Jim E. Horne
    • , Paul White
    • , Andrew J. Wilson
    • , Antreas C. Kalli
    • , Roman Tuma
    • , Alison E. Ashcroft
    • , David J. Brockwell
    •  & Sheena E. Radford
  • Article
    | Open Access

    p53 is an important tumor suppressor protein which is regulated by the E3 ubiquitin ligase MDM2. Here the authors reveal that DNA damage-induced Ser429 phosphorylation of MDM2 serve to boost the activity of MDM2 homodimer by stabilizing the active E2–ubiquitin complex and promote its self-destruction to enable rapid p53 stabilization.

    • Helge M. Magnussen
    • , Syed F. Ahmed
    • , Gary. J. Sibbet
    • , Ventzislava A. Hristova
    • , Koji Nomura
    • , Andreas K. Hock
    • , Lewis J. Archibald
    • , Andrew G. Jamieson
    • , David Fushman
    • , Karen H. Vousden
    • , Allan M. Weissman
    •  & Danny T. Huang
  • Article
    | Open Access

    Shieldin, including SHLD1, SHLD2, SHLD3 and REV7, functions to suppress the DNA termini nucleolytic resection during non-homologous end joining (NHEJ). Here the authors present the crystal structure of the SHLD3-REV7-SHLD2 ternary complex revealing insights into the mechanism of the complex.

    • Ling Liang
    • , Jiawen Feng
    • , Peng Zuo
    • , Juan Yang
    • , Yishuo Lu
    •  & Yuxin Yin
  • Article
    | Open Access

    Flagellin proteins of Salmonella flagella are methylated. Here, the authors show that flagellin methylation facilitates adhesion of Salmonella to hydrophobic host-cell surfaces, and contributes to efficient gut colonization and host infection.

    • Julia A. Horstmann
    • , Michele Lunelli
    • , Hélène Cazzola
    • , Johannes Heidemann
    • , Caroline Kühne
    • , Pascal Steffen
    • , Sandra Szefs
    • , Claire Rossi
    • , Ravi K. Lokareddy
    • , Chu Wang
    • , Laurine Lemaire
    • , Kelly T. Hughes
    • , Charlotte Uetrecht
    • , Hartmut Schlüter
    • , Guntram A. Grassl
    • , Theresia E. B. Stradal
    • , Yannick Rossez
    • , Michael Kolbe
    •  & Marc Erhardt
  • 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
    • , Guijun Shang
    • , Emiko Uchikawa
    • , Hui Tian
    • , Xiao-Chen Bai
    •  & Xuewu Zhang
  • 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
    • , Malay Patra
    • , Radhika Malik
    • , Shahar Nisemblat
    • , Orna Chomsky-Hecht
    • , Avital Parnas
    • , Abdussalam Azem
    • , Joel A. Hirsch
    •  & 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
    • , Benjamin R. Duffus
    • , Jörg Bürger
    • , Tobias Hartmann
    • , Thorsten Mielke
    • , Christian Teutloff
    • , Silke Leimkühler
    •  & Petra Wendler
  • 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
    • , Hikaru Mase
    • , Takuya Otani
    • , Tomoka Kobayashi
    • , Manatsu Tamura
    • , Bruno Kilunga Kubata
    • , Katsuaki Inoue
    • , Robert P. Rambo
    • , Susumu Uchiyama
    • , Kentaro Ishii
    • , Shigenori Nishimura
    •  & Takashi Inui
  • 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
    • , Malik M. Abdullah
    • , Andrew V. Martin
    • , Marco Kloos
    • , Agostino Marinelli
    • , Andrew Aquila
    • , Thomas R. M. Barends
    • , Franz-Josef Decker
    • , R. Bruce Doak
    • , Lutz Foucar
    • , Elisabeth Hartmann
    • , Mario Hilpert
    • , Mark S. Hunter
    • , Zoltan Jurek
    • , Jason E. Koglin
    • , Alexander Kozlov
    • , Alberto A. Lutman
    • , Gabriela Nass Kovacs
    • , Christopher M. Roome
    • , Robert L. Shoeman
    • , Robin Santra
    • , Harry M. Quiney
    • , Beata Ziaja
    • , Sébastien Boutet
    •  & 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
    • , Tatyana Bodrug
    • , Gavin Young
    • , Ryan T. VanderLinden
    • , Brenda A. Schulman
    • , Johannes Schimpf
    • , Thorsten Friedrich
    • , Phat Vinh Dip
    • , Thomas U. Schwartz
    • , Benedikt Bauer
    • , Jan-Michael Peters
    • , Weston B. Struwe
    • , Justin L. P. Benesch
    • , Nicholas G. Brown
    • , David Haselbach
    •  & 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
    • , Yanfei Huang
    • , Dong Li
    • , Youyou Han
    • , Min Chang
    • , Jiaqi Fu
    • , Yongchao Xie
    • , Jie Ren
    • , Hao Wang
    • , Yi Zhang
    • , Zhao-Qing Luo
    •  & Yue Feng
  • Article
    | Open Access

    NifB is a radical SAM enzyme involved in the biosynthesis of the Mo-nitrogenase cofactor, which is responsible for the ambient conversion of N2 to NH3. Here, the authors identify and uncover the function of a His43 residue as an essential nitrogen ligand of NifB in cofactor biosynthesis.

    • Lee A. Rettberg
    • , Jarett Wilcoxen
    • , Andrew J. Jasniewski
    • , Chi Chung Lee
    • , Kazuki Tanifuji
    • , Yilin Hu
    • , R. David Britt
    •  & Markus W. Ribbe