Latest Research

  • 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
  • Article |

    Analysis of the relationships between transcription, replication, and stability of large genes associated with common fragile sites suggests that high transcription levels alleviate genome instability by altering replication timing and allowing cells to complete replication before mitosis.

    • Marion Blin
    • , Benoît Le Tallec
    • , Viola Nähse
    • , Mélanie Schmidt
    • , Caroline Brossas
    • , Gael A. Millot
    • , Marie-Noëlle Prioleau
    •  & Michelle Debatisse
  • Review Article |

    In this Review, Wiedenheft and colleagues retrace events that led from early endeavours to understand the role of Cas9 in CRISPR-mediated adaptive immunity to current efforts aimed at developing this enzyme for programmable genetic editing.

    • Royce A. Wilkinson
    • , Coleman Martin
    • , Artem A. Nemudryi
    •  & Blake Wiedenheft
  • Article |

    Comparative genome-wide analyses reveal that DNA replication origins fire near the initiation site of highly transcribed genes, ensuring co-directional replication and transcription in highly active regions of the human genome.

    • Yu-Hung Chen
    • , Sarah Keegan
    • , Malik Kahli
    • , Peter Tonzi
    • , David Fenyö
    • , Tony T. Huang
    •  & Duncan J. Smith
  • Review Article |

    Zhou, Gaullier and Luger review insights derived from cutting-edge biophysical and structural approaches applied to the study of nucleosome dynamics and nucleosome-binding factors, with a focus on the experimental advances driving the research.

    • Keda Zhou
    • , Guillaume Gaullier
    •  & Karolin Luger
  • Article |

    Rubinstein and colleagues report a structure of the obligate respiratory III2IV2 supercomplex from M. smegmatis, revealing two functionally relevant conformations of the cytochrome cc subunit and a SOD subunit that may detoxify reactive oxygen species.

    • Benjamin Wiseman
    • , Ram Gopal Nitharwal
    • , Olga Fedotovskaya
    • , Jacob Schäfer
    • , Hui Guo
    • , Qie Kuang
    • , Samir Benlekbir
    • , Dan Sjöstrand
    • , Pia Ädelroth
    • , John L Rubinstein
    • , Peter Brzezinski
    •  & Martin Högbom
  • Article |

    A combination of proteomics and structural analyses reveals the assembly mechanism of transcription factor TFIID in human cells and identifies the chaperonin CCT as a checkpoint in the process.

    • Simona V. Antonova
    • , Matthias Haffke
    • , Eleonora Corradini
    • , Mykolas Mikuciunas
    • , Teck Y. Low
    • , Luca Signor
    • , Robert M. van Es
    • , Kapil Gupta
    • , Elisabeth Scheer
    • , Harmjan R. Vos
    • , László Tora
    • , Albert J. R. Heck
    • , H. T. Marc Timmers
    •  & Imre Berger
  • Article |

    Point centromeres of budding yeast direct binding of a CBF3 complex that recruits the centromere-specific Cse4 nucleosome to CEN loci. A cryo-EM structure of CBF3 bound to its cognate CDEIII element and a model of the CBF3–Cse4–CEN complex reveal interactions underlying kinetochore assembly.

    • Kaige Yan
    • , Ziguo Zhang
    • , Jing Yang
    • , Stephen H. McLaughlin
    •  & David Barford
  • Article |

    Single-molecule magnetic tweezers analyses and supporting MD simulations provide evidence for protein-gate opening of type IA topoisomerases.

    • Maria Mills
    • , Yuk-Ching Tse-Dinh
    •  & Keir C. Neuman
  • Article |

    The lncRNA SAMMSON promotes a balanced increase in rRNA maturation and protein synthesis in the cytosol and mitochondria by modulating the localization of CARF, which affects two rRNA-processing factors.

    • Roberto Vendramin
    • , Yvessa Verheyden
    • , Hideaki Ishikawa
    • , Lucas Goedert
    • , Emilien Nicolas
    • , Kritika Saraf
    • , Alexandros Armaos
    • , Riccardo Delli Ponti
    • , Keichi Izumikawa
    • , Pieter Mestdagh
    • , Denis L. J. Lafontaine
    • , Gian Gaetano Tartaglia
    • , Nobuhiro Takahashi
    • , Jean-Christophe Marine
    •  & Eleonora Leucci
  • Review Article |

    In this Review, Haoxing Xu and colleagues summarize current knowledge of TRP channels and their roles in the response to environmental and cellular signals, focusing in particular on the least known class, the organellar TRPs.

    • Xiaoli Zhang
    • , Meiqin Hu
    • , Yexin Yang
    •  & Haoxing Xu
  • Article |

    Baker, Marcos and colleagues analyze β-arches (loops connecting unpaired β-strands) and derive rules used for de novo design of a hyperthermostable jellyroll structure, with eight antiparallel β-strands forming double-stranded β-helices.

    • Enrique Marcos
    • , Tamuka M. Chidyausiku
    • , Andrew C. McShan
    • , Thomas Evangelidis
    • , Santrupti Nerli
    • , Lauren Carter
    • , Lucas G. Nivón
    • , Audrey Davis
    • , Gustav Oberdorfer
    • , Konstantinos Tripsianes
    • , Nikolaos G. Sgourakis
    •  & David Baker
  • Article |

    A new class of miRNA-recognition elements that function exclusively in protein-coding regions use distinct target-recognition rules and mediate translational repression instead of mRNA destabilization.

    • Kai Zhang
    • , Xiaorong Zhang
    • , Zhiqiang Cai
    • , Jie Zhou
    • , Ran Cao
    • , Ya Zhao
    • , Zonggui Chen
    • , Dehe Wang
    • , Wen Ruan
    • , Qian Zhao
    • , Guangqiao Liu
    • , Yuanchao Xue
    • , Yan Qin
    • , Bing Zhou
    • , Ligang Wu
    • , Timothy Nilsen
    • , Yu Zhou
    •  & Xiang-Dong Fu
  • Article |

    Crystal structures of human σ1 receptor bound to the antagonists haloperidol and NE-100, and to agonist (+)-pentazocine, alongside MD simulations, reveal a unique binding pose for, and major conformational rearrangements induced by, the agonist.

    • Hayden R. Schmidt
    • , Robin M. Betz
    • , Ron O. Dror
    •  & Andrew C. Kruse
  • Article |

    A combination of fluorescence approaches that permit conformational changes of SNARE proteins to be visualized in different lipid environments reveals interactions underlying vesicle–membrane fusion.

    • Volker Kiessling
    • , Alex J. B. Kreutzberger
    • , Binyong Liang
    • , Sarah B. Nyenhuis
    • , Patrick Seelheim
    • , J. David Castle
    • , David S. Cafiso
    •  & Lukas K. Tamm
  • Article |

    Crystal structures of the Ku70/80–DNA complex with Ku binding motifs of APLF and XLF reveal distinct interaction sites and an induced conformational change in Ku80 critical for function in NHEJ repair.

    • Clement Nemoz
    • , Virginie Ropars
    • , Philippe Frit
    • , Amandine Gontier
    • , Pascal Drevet
    • , Jinchao Yu
    • , Raphaël Guerois
    • , Aurelien Pitois
    • , Audrey Comte
    • , Christine Delteil
    • , Nadia Barboule
    • , Pierre Legrand
    • , Sonia Baconnais
    • , Yandong Yin
    • , Satish Tadi
    • , Emeline Barbet-Massin
    • , Imre Berger
    • , Eric Le Cam
    • , Mauro Modesti
    • , Eli Rothenberg
    • , Patrick Calsou
    •  & Jean Baptiste Charbonnier
  • Article |

    Histone variant macroH2A is initially pervasively deposited across the mouse genome and is subsequently selectively evicted from transcriptionally active regions to establish macroH2A chromatin domains.

    • Zhen Sun
    • , Dan Filipescu
    • , Joshua Andrade
    • , Alexandre Gaspar-Maia
    • , Beatrix Ueberheide
    •  & Emily Bernstein
  • Article |

    Biochemical and genome-wide analyses reveal that G4 structures sequester and inhibit the activity of DNMT1, thereby protecting CpG islands from methylation in human cells.

    • Shi-Qing Mao
    • , Avazeh T. Ghanbarian
    • , Jochen Spiegel
    • , Sergio Martínez Cuesta
    • , Dario Beraldi
    • , Marco Di Antonio
    • , Giovanni Marsico
    • , Robert Hänsel-Hertsch
    • , David Tannahill
    •  & Shankar Balasubramanian
  • Perspective |

    Nichols and Corces summarize the current knowledge of SMC structure and function and propose a new mechanism for SMC motor activity, which is central to the DNA loop extrusion model of genome organization.

    • Michael H. Nichols
    •  & Victor G. Corces
  • Article |

    Cryo-EM data and functional assays reveal how the actin-cross-linking protein filamin A interacts with F-actin, rationalizing human disease mutations in molecular detail.

    • Daniel V. Iwamoto
    • , Andrew Huehn
    • , Bertrand Simon
    • , Clotilde Huet-Calderwood
    • , Massimiliano Baldassarre
    • , Charles V. Sindelar
    •  & David A. Calderwood
  • Article |

    Structural, biochemical, and modeling studies reveal how the non-canonical RNA Pol II subunit Gdown1 precludes general transcription factor interactions with Pol II(G) to repress transcriptional activity in the absence of Mediator.

    • Miki Jishage
    • , Xiaodi Yu
    • , Yi Shi
    • , Sai J. Ganesan
    • , Wei-Yi Chen
    • , Andrej Sali
    • , Brian T. Chait
    • , Francisco J. Asturias
    •  & Robert G. Roeder
  • Article |

    Cryo-EM and electrophysiological studies of two mechanosensitive OSCA channels from Arabidopsis thaliana reveal their structural similarity to osmosensitive TMEM16 channels and suggest they are gated by force from lipid in response to osmotic stress.

    • Mingfeng Zhang
    • , Dali Wang
    • , Yunlu Kang
    • , Jing-Xiang Wu
    • , Fuqiang Yao
    • , Chengfang Pan
    • , Zhiqiang Yan
    • , Chen Song
    •  & Lei Chen
  • Review Article |

    Cramer and colleagues review and discuss how the structural elucidation of transcription factors and functional complexes of human mitochondrial RNA polymerase have informed emerging understanding of the mechanism of mitochondrial gene transcription.

    • Hauke S. Hillen
    • , Dmitry Temiakov
    •  & Patrick Cramer
  • Article |

    Single-molecule and biochemistry approaches are used to investigate how ultra-fine DNA bridges, which form between sister chromatids during anaphase, are recognized and processed by cellular factors PICH, BLM, TopoIIIα and RPA.

    • Kata Sarlós
    • , Andreas S. Biebricher
    • , Anna H. Bizard
    • , Julia A. M. Bakx
    • , Anna G. Ferreté-Bonastre
    • , Mauro Modesti
    • , Manikandan Paramasivam
    • , Qi Yao
    • , Erwin J. G. Peterman
    • , Gijs J. L. Wuite
    •  & Ian D. Hickson
  • Article |

    Influenza A virus (IAV) infection induces transcription termination defects in host cells, an effect modulated by SUMOylation of an intrinsically disordered region of the influenza NS1 protein expressed by the 1918 pandemic IAV strain.

    • Nan Zhao
    • , Vittorio Sebastiano
    • , Natasha Moshkina
    • , Nacho Mena
    • , Judd Hultquist
    • , David Jimenez-Morales
    • , Yixuan Ma
    • , Alex Rialdi
    • , Randy Albrecht
    • , Romain Fenouil
    • , Maria Teresa Sánchez-Aparicio
    • , Juan Ayllon
    • , Sweta Ravisankar
    • , Bahareh Haddad
    • , Jessica Sook Yuin Ho
    • , Diana Low
    • , Jian Jin
    • , Vyacheslav Yurchenko
    • , Rab K. Prinjha
    • , Alexander Tarakhovsky
    • , Massimo Squatrito
    • , Dalila Pinto
    • , Kimaada Allette
    • , Minji Byun
    • , Melissa Laird Smith
    • , Robert Sebra
    • , Ernesto Guccione
    • , Terrence Tumpey
    • , Nevan Krogan
    • , Benjamin Greenbaum
    • , Harm van Bakel
    • , Adolfo García-Sastre
    •  & Ivan Marazzi
  • Article |

    X-ray crystal structures and mutational analysis of the Arp8 module of the yeast chromatin remodeler INO80 reveal its function as a linker DNA sensor required for nucleosome positioning.

    • Kilian R. Knoll
    • , Sebastian Eustermann
    • , Vanessa Niebauer
    • , Elisa Oberbeckmann
    • , Gabriele Stoehr
    • , Kevin Schall
    • , Alessandro Tosi
    • , Marianne Schwarz
    • , Andrea Buchfellner
    • , Philipp Korber
    •  & Karl-Peter Hopfner
  • Article |

    Structural and biochemical analyses identify the ZZ domain of p300 as a novel histone H3–binding module that promotes p300 chromatin association and is required for selective acetylation of H3K18 and H3K27 in human cells.

    • Yi Zhang
    • , Yongming Xue
    • , Jiejun Shi
    • , JaeWoo Ahn
    • , Wenyi Mi
    • , Muzaffar Ali
    • , Xiaolu Wang
    • , Brianna J. Klein
    • , Hong Wen
    • , Wei Li
    • , Xiaobing Shi
    •  & Tatiana G. Kutateladze
  • Article |

    The interactions between HIV-1 Env and host cell receptors CD4 and CCR5 or CXCR4 are examined using direct stochastic optical reconstruction microscopy and fluorescence fluctuation spectroscopy imaging, revealing a dynamic three-step process leading to formation of the pre-fusion complex.

    • Maro Iliopoulou
    • , Rory Nolan
    • , Luis Alvarez
    • , Yasunori Watanabe
    • , Charles A. Coomer
    • , G. Maria Jakobsdottir
    • , Thomas A. Bowden
    •  & Sergi Padilla-Parra