Browse Articles

  • 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
  • News & Views |

    Autophagy is a highly contextual modulator of tumorigenesis. A new study shows that autophagy can serve as a tumor suppressor to mediate cell death at replicative crisis.

    • Masashi Narita
  • 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
  • News & Views |

    Structural information on the respiratory supercomplex III2IV2 from budding yeast and from Mycobacterium smegmatis has become available, with cryo-EM work from four different groups.

    • Joana S. Sousa
    •  & Janet Vonck
  • News & Views |

    A growing body of evidence suggests that cotranslational folding occurs from bacteria to mammalian cells, in particular for multi-domain proteins. In the assembly of yeast proteasomes, the initial interaction of Rpt1 and Rpt2 subunits has been found to take place on the translating ribosomes, coordinated by elongation pausing and involving the formation of Not1-containing compartments.

    • Xiao-Min Liu
    •  & Shu-Bing Qian
  • 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
  • Meeting Report |

    The Ninth International Conference on the Hsp90 Chaperone Machine concluded in October 2018, in Leysin, Switzerland. The program highlighted findings in various areas, including integrated insights into the molecular mechanism of Hsp90, cochaperones, and clients’ structure and function.

    • Laura J. Blair
    • , Olivier Genest
    •  & Mehdi Mollapour
  • 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
  • News & Views |

    The intertwined structure of the Taf5–Taf6–Taf9 subcomplex is dependent on the chaperonin CCT for its assembly and subsequent integration into the general transcription factor TFIID.

    • Alan C. M. Cheung
  • 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
  • News & Views |

    Recent advances in the ability to detect mRNA base modifications have led to a renewed appreciation for the diversity of the epitranscriptome and its ability to influence gene expression. Now, a study in Cell adds acetylated cytidine (ac4C) to the list, identifying it as a widespread mark in cellular mRNAs that influences both mRNA stability and translation.

    • Seung H. Choi
    •  & Kate D. Meyer
  • 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
  • News & Views |

    Attempts to develop a method for 3D genome reconstruction of single cells have been frustrated by the inability to distinguish between chromosome homologs. A novel Hi-C workflow uses haplotype imputation to map the nuclear organization of single diploid cells.

    • Blake A. Caldwell
    •  & Marisa S. Bartolomei
  • 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
  • Meeting Report |

    Cells rely on the synthesis, translocation, folding and turnover of proteins. Owing to complexity, spatiotemporal regulation and surveillance of these processes are vital. Advances in the field were discussed at the international symposium ‘Proteins: From the Cradle to the Grave’ that took place in the wonderful setting of a Buddhist temple located close to Kyoto, Japan. The emerging theme was the interdependence among cellular processes and organelle compartments.

    • Johannes M. Herrmann
    • , Pedro Carvalho
    • , Manajit Hayer-Hartl
    •  & Tohru Yoshihisa
  • 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
  • News & Views |

    The σ1 receptor, an endoplasmic reticulum–resident transmembrane protein, modulates many physiological and pathological processes and binds multiple drugs, but is nonetheless poorly understood. In a recent issue, Kruse and colleagues illustrate structural differences between agonist- and antagonist-bound receptor and propose that agonist binding may impair oligomerization, making a major step in understanding σ1 function. They also use a combination of kinetic and molecular dynamic modeling to explain how ligands access the binding pocket.

    • Felix J. Kim
    •  & Gavril W. Pasternak
  • 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