Latest Research

  • 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
  • Resource |

    A quantitative atlas of RNA m5C sites in human and mouse tissues based on a new discovery pipeline allows the identification of sequence motifs and structural features associated with the modification and provides a resource for future studies.

    • Tao Huang
    • , Wanying Chen
    • , Jianheng Liu
    • , Nannan Gu
    •  & Rui Zhang
  • 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
  • Resource |

    Structure maps of RNAs localized to chromatin, nucleoplasm and cytoplasm provide a rich resource with which to investigate the interplay of RNA structure, RNA–protein interactions and RNA modifications.

    • Lei Sun
    • , Furqan M. Fazal
    • , Pan Li
    • , James P. Broughton
    • , Byron Lee
    • , Lei Tang
    • , Wenze Huang
    • , Eric T. Kool
    • , Howard Y. Chang
    •  & Qiangfeng Cliff Zhang
  • 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
  • Article |

    Comparative Hi-C analysis of synchronized mouse spermatocyte populations reveals dynamic changes in chromosome organization during meiotic prophase that permit homolog pairing while sustaining gene expression.

    • Lucas Patel
    • , Rhea Kang
    • , Scott C. Rosenberg
    • , Yunjiang Qiu
    • , Ramya Raviram
    • , Sora Chee
    • , Rong Hu
    • , Bing Ren
    • , Francesca Cole
    •  & Kevin D. Corbett
  • Article |

    Structures of human 5-HT2AR in complex with several drugs reveal a side-extended cavity that is unique for this receptor, while molecular docking suggests that a highly 5-HT2AR-selective antagonist binds residues within this cavity.

    • Kanako Terakado Kimura
    • , Hidetsugu Asada
    • , Asuka Inoue
    • , Francois Marie Ngako Kadji
    • , Dohyun Im
    • , Chihiro Mori
    • , Takatoshi Arakawa
    • , Kunio Hirata
    • , Yayoi Nomura
    • , Norimichi Nomura
    • , Junken Aoki
    • , So Iwata
    •  & Tatsuro Shimamura
  • Article |

    A combination of bulk and single-molecule fluorescence analysis reveals the choreography of binding and rearrangement of individual DNA-binding domains of RPA during homologous recombination.

    • Nilisha Pokhrel
    • , Colleen C. Caldwell
    • , Elliot I. Corless
    • , Emma A. Tillison
    • , Joseph Tibbs
    • , Nina Jocic
    • , S. M. Ali Tabei
    • , Marc S. Wold
    • , Maria Spies
    •  & Edwin Antony
  • Article |

    Assembly of proteasome subunits Rpt1 and Rpt2 is shown to occur co-translationally. Ribosomal pausing facilitates the incorporation of nascent Rpt1 and Rpt2 into Not-containing particles and their subsequent association with each other.

    • Olesya O. Panasenko
    • , Syam Prakash Somasekharan
    • , Zoltan Villanyi
    • , Marina Zagatti
    • , Fedor Bezrukov
    • , Ravish Rashpa
    • , Julien Cornut
    • , Jawad Iqbal
    • , Marion Longis
    • , Sarah H. Carl
    • , Cohue Peña
    • , Vikram G. Panse
    •  & Martine A. Collart
  • Article |

    The noncoding RNA Xist regulates the accessibility of select chromatin regions on the inactive X chromosome (Xi) by directly inhibiting the chromosome remodeler BRG1 and by expelling it from the Xi.

    • Teddy Jégu
    • , Roy Blum
    • , Jesse C. Cochrane
    • , Lin Yang
    • , Chen-Yu Wang
    • , Maud-Emmanuelle Gilles
    • , David Colognori
    • , Attila Szanto
    • , Sharon K. Marr
    • , Robert E. Kingston
    •  & Jeannie T. Lee
  • Article |

    The cryo-EM structure of budding yeast supercomplex III2IV2 is now presented, providing molecular details of CIV (also known as cytochrome c oxidase) and revealing notable differences with mammalian systems.

    • Andrew M. Hartley
    • , Natalya Lukoyanova
    • , Yunyi Zhang
    • , Alfredo Cabrera-Orefice
    • , Susanne Arnold
    • , Brigitte Meunier
    • , Nikos Pinotsis
    •  & Amandine Maréchal
  • Article |

    Structures of yeast mitochondrial supercomplexes III2IV and III2IV2 are determined by cryo-EM, revealing the interactions between CIII and CIV and an overall different architecture compared to mammalian assemblies.

    • Sorbhi Rathore
    • , Jens Berndtsson
    • , Lorena Marin-Buera
    • , Julian Conrad
    • , Marta Carroni
    • , Peter Brzezinski
    •  & Martin Ott