Articles

  • Article |

    X-ray crystal structures of the full-length TcdB exotoxin of bacterial pathogen Clostridium difficile reveal pH-dependent conformational changes that allow translocation of the toxin from endosomes into the cytosol.

    • Peng Chen
    • , Kwok-ho Lam
    • , Zheng Liu
    • , Frank A. Mindlin
    • , Baohua Chen
    • , Craig B. Gutierrez
    • , Lan Huang
    • , Yongrong Zhang
    • , Therwa Hamza
    • , Hanping Feng
    • , Tsutomu Matsui
    • , Mark E. Bowen
    • , Kay Perry
    •  & Rongsheng Jin
  • Article |

    AAA+ ATPase spastin recognizes tubulin polyglutamylated C-terminal tails and severs microtubules. A cryo-EM structure of fly spastin with polyGlu reveals how spastin engages with the substrate, an activity allosterically coupled to nucleotide binding and oligomerization.

    • Colby R. Sandate
    • , Agnieszka Szyk
    • , Elena A. Zehr
    • , Gabriel C. Lander
    •  & Antonina Roll-Mecak
  • Article |

    O-Mannosylation is an essential protein modification implicated in several diseases. Cryo-EM structures of the yeast mannosyltransferase complex Pmt1–Pmt2 bound to substrates reveal the substrate recognition model and confirm the reaction mechanism.

    • Lin Bai
    • , Amanda Kovach
    • , Qinglong You
    • , Alanna Kenny
    •  & Huilin Li
  • Article |

    Cryo-EM structures of the active Cas9–sgRNA–DNA complex in the presence of Mg2+ capture Cas9 in the pre- and postcatalytic states as well as in the product-bound state, and reveal coupled domain motions and interactions between the enzyme and nucleic acids.

    • Xing Zhu
    • , Ryan Clarke
    • , Anupama K. Puppala
    • , Sagar Chittori
    • , Alan Merk
    • , Bradley J. Merrill
    • , Miljan Simonović
    •  & Sriram Subramaniam
  • Article |

    A CDK multisite phosphorylation code ensures that CDK can signal via hundreds of distinct targets to provide a temporally ordered phosphorylation pattern required for proper execution of the cell cycle.

    • Mihkel Örd
    • , Kaidi Möll
    • , Alissa Agerova
    • , Rait Kivi
    • , Ilona Faustova
    • , Rainis Venta
    • , Ervin Valk
    •  & Mart Loog
  • Article |

    Crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal α-tubulin peptide define the structural basis of tubulin detyrosination.

    • Na Wang
    • , Christophe Bosc
    • , Sung Ryul Choi
    • , Benoit Boulan
    • , Leticia Peris
    • , Natacha Olieric
    • , Hongyu Bao
    • , Fatma Krichen
    • , Liu Chen
    • , Annie Andrieux
    • , Vincent Olieric
    • , Marie-Jo Moutin
    • , Michel O. Steinmetz
    •  & Hongda Huang
  • Article |

    A solid-state NMR structure of an amyloid fibril formed by synthetic human glucagon reveals two distinct β-strand conformations that alternate in an antiparallel fashion along the fibril axis.

    • Martin D. Gelenter
    • , Katelyn J. Smith
    • , Shu-Yu Liao
    • , Venkata S. Mandala
    • , Aurelio J. Dregni
    • , Matthew S. Lamm
    • , Yu Tian
    • , Wei Xu
    • , Darrin J. Pochan
    • , Thomas J. Tucker
    • , Yongchao Su
    •  & Mei Hong
  • Article |

    Structures of human equilibrative nucleoside transporter 1 in complex with either dilazep or NBMPR reveal distinct inhibitory mechanisms of these drugs, providing insight for rational design of improved therapeutics modulating nucleoside transport.

    • Nicholas J. Wright
    •  & Seok-Yong Lee
  • Article |

    Cryo-EM structures of fibrils formed by two segments from TDP-43 that are essential for aggregation of the full-length protein reveal fibril polymorphism and suggest mechanisms for pathogenesis.

    • Qin Cao
    • , David R. Boyer
    • , Michael R. Sawaya
    • , Peng Ge
    •  & David S. Eisenberg
  • Article |

    HMCES protects abasic sites that block DNA replication via covalent protein attachment. Crystal structures of the Escherichia coli HMCES homolog YedK reveal that the conserved SRAP domain forms a thiazolidine linkage with the abasic site, explaining the stability of the DNA-protein cross-link and its specificity for DNA lesions at stalled replication forks.

    • Petria S. Thompson
    • , Katherine M. Amidon
    • , Kareem N. Mohni
    • , David Cortez
    •  & Brandt F. Eichman
  • Article |

    Crystal structures of human VASH1–SVBP alone, in complex with a tyrosine-derived covalent inhibitor and bound to parthenolide, explain the requirement for SVBP during tubulin detyrosination and reveal the basis for substrate recognition.

    • Faxiang Li
    • , Yingjie Hu
    • , Shutao Qi
    • , Xuelian Luo
    •  & Hongtao Yu
  • Article |

    The previously unknown human prenyltransferase, GGTase3, geranylgeranylates the ubiquitin ligase FBXL2, which bears a motif predicted to be recognized by GGTase1. The structure of the GGTase3–FBXL2–SKP1 complex reveals the basis of GGTase3 substrate specificity.

    • Shafi Kuchay
    • , Hui Wang
    • , Antonio Marzio
    • , Kunj Jain
    • , Harrison Homer
    • , Nicole Fehrenbacher
    • , Mark R. Philips
    • , Ning Zheng
    •  & Michele Pagano
  • Article |

    Otopetrins are proton channels and candidate sour taste receptors. Cryo-EM structures of zebrafish Otop1 and chicken Otop3 reveal potential proton conduction pathways.

    • Kei Saotome
    • , Bochuan Teng
    • , Che Chun (Alex) Tsui
    • , Wen-Hsin Lee
    • , Yu-Hsiang Tu
    • , Joshua P. Kaplan
    • , Mark S. P. Sansom
    • , Emily R. Liman
    •  & Andrew B. Ward
  • Article |

    X-ray crystallography and cryo-EM analyses capture the influenza RNA polymerase with RNA primer-template at distinct steps of initiation and elongation, revealing changes in its active site that promote viral RNA synthesis.

    • Tomas Kouba
    • , Petra Drncová
    •  & Stephen Cusack
  • Article |

    Structures of PF846-stalled human ribosome nascent chain complexes show that this drug-like molecule binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S rRNA and alters the path of the nascent polypeptide chain.

    • Wenfei Li
    • , Fred R. Ward
    • , Kim F. McClure
    • , Stacey Tsai-Lan Chang
    • , Elizabeth Montabana
    • , Spiros Liras
    • , Robert G. Dullea
    •  & Jamie H. D. Cate
  • Article |

    Structural and functional analyses reveal how 9-O-acetyl sialic acid is recognized by the human coronavirus OC43 S glycoprotein and how this interaction promotes viral entry.

    • M. Alejandra Tortorici
    • , Alexandra C. Walls
    • , Yifei Lang
    • , Chunyan Wang
    • , Zeshi Li
    • , Danielle Koerhuis
    • , Geert-Jan Boons
    • , Berend-Jan Bosch
    • , Félix A. Rey
    • , Raoul J. de Groot
    •  & David Veesler
  • Article |

    Cryo-EM structure of the LAT1–CD98hc heterodimer in complex with two antibodies offers insights into the assembly and function of LAT1–CD98hc, and reveals the epitopes targeted by the potentially therapeutic antibodies with an antitumor activity.

    • Yongchan Lee
    • , Pattama Wiriyasermkul
    • , Chunhuan Jin
    • , Lili Quan
    • , Ryuichi Ohgaki
    • , Suguru Okuda
    • , Tsukasa Kusakizako
    • , Tomohiro Nishizawa
    • , Kazumasa Oda
    • , Ryuichiro Ishitani
    • , Takeshi Yokoyama
    • , Takanori Nakane
    • , Mikako Shirouzu
    • , Hitoshi Endou
    • , Shushi Nagamori
    • , Yoshikatsu Kanai
    •  & Osamu Nureki
  • Article |

    Cyanobacteria express IsiA, a photosystem I antenna, in response to stress. The structure of the photosystem I–IsiA complex reveals flexibility of the interactions within the complex and suggests the mechanism of energy transfer.

    • Hila Toporik
    • , Jin Li
    • , Dewight Williams
    • , Po-Lin Chiu
    •  & Yuval Mazor
  • Article |

    A single-molecule FISH-based method to quantify splicing efficiency at active transcription sites in single cells reveals an unexpected ‘economy of scale’ behavior in which splicing efficiency increases with transcription rate.

    • Fangyuan Ding
    •  & Michael B. Elowitz
  • Article |

    A modified version of DamID allows measurement of chromosomal interactions without crosslinking and ligation, and provides validation for the existence of TADs in mESCs.

    • Josef Redolfi
    • , Yinxiu Zhan
    • , Christian Valdes-Quezada
    • , Mariya Kryzhanovska
    • , Isabel Guerreiro
    • , Vytautas Iesmantavicius
    • , Tim Pollex
    • , Ralph S. Grand
    • , Eskeatnaf Mulugeta
    • , Jop Kind
    • , Guido Tiana
    • , Sebastien A. Smallwood
    • , Wouter de Laat
    •  & Luca Giorgetti
  • Article |

    Chris Garcia, David Baker and colleagues use a computational approach to develop designed repeat protein binders (DRPBs), which function as human Frizzled (Fz) subtype-selective antagonists and enable identification of Fz subtypes active in different organs.

    • Luke T. Dang
    • , Yi Miao
    • , Andrew Ha
    • , Kanako Yuki
    • , Keunwan Park
    • , Claudia Y. Janda
    • , Kevin M. Jude
    • , Kritika Mohan
    • , Nhi Ha
    • , Mario Vallon
    • , Jenny Yuan
    • , José G. Vilches-Moure
    • , Calvin J. Kuo
    • , K. Christopher Garcia
    •  & David Baker
  • Article |

    KMT9, a new histone lysine methyltransferase targeting H4K12, is enriched at promoters of genes encoding molecules involved in the cell cycle and controls the growth of androgen receptor–dependent and castration- and enzalutamide-resistant prostate cancer cells and xenograft tumors.

    • Eric Metzger
    • , Sheng Wang
    • , Sylvia Urban
    • , Dominica Willmann
    • , Andreas Schmidt
    • , Anne Offermann
    • , Anita Allen
    • , Manuela Sum
    • , Nadine Obier
    • , Félicie Cottard
    • , Svenja Ulferts
    • , Bogdan-Tiberius Preca
    • , Bianca Hermann
    • , Jochen Maurer
    • , Holger Greschik
    • , Veit Hornung
    • , Oliver Einsle
    • , Sven Perner
    • , Axel Imhof
    • , Manfred Jung
    •  & Roland Schüle
  • Article |

    Takagi and colleagues report the crystal structure of human Wnt3 in complex with the mouse Frizzled 8 Cys-rich domain, a structural model of the Wnt–Frizzled–LRP6 ternary complex and engineered tagged versions of Wnt3a that retain biological function.

    • Hidenori Hirai
    • , Kyoko Matoba
    • , Emiko Mihara
    • , Takao Arimori
    •  & Junichi Takagi
  • Article |

    During ribosome-associated quality control (RQC), ANKZF1 severs polypeptidyl-tRNAs on RQC complexes by cleaving the terminal 3′CCA nucleotides, which leads to tRNA fragments that are ‘quality checked’ and recycled in the cytosol.

    • Matthew C. J. Yip
    • , Alexander F. A. Keszei
    • , Qing Feng
    • , Vincent Chu
    • , Michael J. McKenna
    •  & Sichen Shao
  • Article |

    Doudna and colleagues determine the mechanisms used by type V anti-CRISPR proteins. AcrVA1 is a multiple-turnover inhibitor that triggers cleavage of the Cas12a-bound guide RNA, while AcrVA4 and AcrVA5 inhibit recognition of dsDNA.

    • Gavin J. Knott
    • , Brittney W. Thornton
    • , Marco J. Lobba
    • , Jun-Jie Liu
    • , Basem Al-Shayeb
    • , Kyle E. Watters
    •  & Jennifer A. Doudna
  • Article |

    Zhiwei Huang and colleagues report structural and biochemical data showing that the anti-CRISPR protein AcrVA5 functions as an acetyltransferase, modifying MbCas12a at Lys635, a residue required for PAM recognition. Acetylation of Lys635 creates a steric clash that prevents binding of target DNA.

    • Liyong Dong
    • , Xiaoyu Guan
    • , Ningning Li
    • , Fan Zhang
    • , Yuwei Zhu
    • , Kuan Ren
    • , Ling Yu
    • , Fengxia Zhou
    • , Zhifu Han
    • , Ning Gao
    •  & Zhiwei Huang
  • Article |

    PICH and Topoisomerase 3a together introduce positive supercoiling into DNA, which could aid efficient sister-chromatid disjunction during mitosis.

    • Anna H. Bizard
    • , Jean-Francois Allemand
    • , Tue Hassenkam
    • , Manikandan Paramasivam
    • , Kata Sarlós
    • , Manika Indrajit Singh
    •  & Ian D. Hickson
  • Article |

    Structural and biochemical data suggest that the essential autophagy protein Atg2 acts as a lipid-transfer protein that supplies phospholipids from the source organelle (especially the ER) to the isolation membranes (IMs) for autophagosome formation.

    • Takuo Osawa
    • , Tetsuya Kotani
    • , Tatsuya Kawaoka
    • , Eri Hirata
    • , Kuninori Suzuki
    • , Hitoshi Nakatogawa
    • , Yoshinori Ohsumi
    •  & Nobuo N. Noda
  • Article |

    ATG12 and ATG5 are covalently conjugated during autophagy. Exceptions are now uncovered: in Plasmodium and Toxoplasma species and in yeast Komagataella phaffii (previously Pichia pastoris), ATG12 and ATG5 form a non-covalent yet functional complex.

    • Yu Pang
    • , Hayashi Yamamoto
    • , Hirokazu Sakamoto
    • , Masahide Oku
    • , Joe Kimanthi Mutungi
    • , Mayurbhai Himatbhai Sahani
    • , Yoshitaka Kurikawa
    • , Kiyoshi Kita
    • , Nobuo N. Noda
    • , Yasuyoshi Sakai
    • , Honglin Jia
    •  & Noboru Mizushima
  • Article |

    The cryo-EM structure of the Saccharomyces cerevisiae 80S ribosome–Xrn1 nuclease complex reveals how the conserved core of Xrn1 allows binding at the mRNA exit channel of the ribosome, ensuring efficient degradation of mRNA after the final round of translation.

    • Petr Tesina
    • , Elisabeth Heckel
    • , Jingdong Cheng
    • , Micheline Fromont-Racine
    • , Robert Buschauer
    • , Lukas Kater
    • , Birgitta Beatrix
    • , Otto Berninghausen
    • , Alain Jacquier
    • , Thomas Becker
    •  & Roland Beckmann
  • Article |

    After acute agonist stimulation, phase-separated complexes form at estrogen-receptor-bound enhancer sites and coalesce into condensates with cooperative enhancer activity. Chronic stimulation causes the condensates to mature into a less dynamic, gel-like state.

    • Sreejith J. Nair
    • , Lu Yang
    • , Dario Meluzzi
    • , Soohwan Oh
    • , Feng Yang
    • , Meyer J. Friedman
    • , Susan Wang
    • , Tom Suter
    • , Ibraheem Alshareedah
    • , Amir Gamliel
    • , Qi Ma
    • , Jie Zhang
    • , Yiren Hu
    • , Yuliang Tan
    • , Kenneth A. Ohgi
    • , Ranveer Singh Jayani
    • , Priya R. Banerjee
    • , Aneel K. Aggarwal
    •  & Michael G. Rosenfeld
  • Article |

    The crystal structure of a broadly neutralizing monoclonal antibody against Ebola virus glycoprotein isolated from a human survivor allows the engineering of variant antibodies with expanded activity and has implications for vaccine design.

    • Brandyn R. West
    • , Anna Z. Wec
    • , Crystal L. Moyer
    • , Marnie L. Fusco
    • , Philipp A. Ilinykh
    • , Kai Huang
    • , Ariel S. Wirchnianski
    • , Rebekah M. James
    • , Andrew S. Herbert
    • , Sean Hui
    • , Eileen Goodwin
    • , Katie A. Howell
    • , Shweta Kailasan
    • , M. Javad Aman
    • , Laura M. Walker
    • , John M. Dye
    • , Alexander Bukreyev
    • , Kartik Chandran
    •  & Erica Ollmann Saphire
  • Article |

    Two evolutionarily distant SMC–kleisin complexes are shown to contain a bendable coiled-coil discontinuity near the middle of their arms, which permits a folded conformation with potential implications for DNA loading and translocation.

    • Frank Bürmann
    • , Byung-Gil Lee
    • , Thane Than
    • , Ludwig Sinn
    • , Francis J O’Reilly
    • , Stanislau Yatskevich
    • , Juri Rappsilber
    • , Bin Hu
    • , Kim Nasmyth
    •  & Jan Löwe
  • Article |

    Histone variant macroH2A1.2 and chromatin remodeler ATRX act jointly to maintain telomere integrity under conditions of acute replication stress in ALT-positive cancer cells.

    • Jeongkyu Kim
    • , Chongkui Sun
    • , Andy D. Tran
    • , Pei-Ju Chin
    • , Penelope D. Ruiz
    • , Kun Wang
    • , Richard J. Gibbons
    • , Matthew J. Gamble
    • , Yie Liu
    •  & Philipp Oberdoerffer
  • Article |

    In vivo and in vitro protein-RNA interaction maps identify an RNA-binding patch within the allosteric regulatory site of PRC2 that explains how RNA-mediated inhibition of PRC2 is relieved by allosteric activation.

    • Qi Zhang
    • , Nicholas J. McKenzie
    • , Robert Warneford-Thomson
    • , Emma H. Gail
    • , Sarena F. Flanigan
    • , Brady M. Owen
    • , Richard Lauman
    • , Vitalina Levina
    • , Benjamin A. Garcia
    • , Ralf B. Schittenhelm
    • , Roberto Bonasio
    •  & Chen Davidovich
  • Article |

    Mechanical distortion of DNA structure induces off-target binding and cleavage by SpyCas9 at sites with up to ten mismatches, a potential mechanism that exposes cryptic off-target sites in cells during transcription or replication.

    • Matthew D. Newton
    • , Benjamin J. Taylor
    • , Rosalie P. C. Driessen
    • , Leonie Roos
    • , Nevena Cvetesic
    • , Shenaz Allyjaun
    • , Boris Lenhard
    • , Maria Emanuela Cuomo
    •  & David S. Rueda