Browse Articles

  • 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
  • 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
  • News & Views |

    RNA uridylation offers a basis for diverse post-transcriptional regulation. Two recent studies reveal new roles of uridylation in immune defense against viruses and retrotransposons.

    • Jinah Yeo
    •  & V. Narry Kim
  • 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
  • Meeting Report |

    A symposium in June 2018 sponsored by the Center on Membrane Protein Production and Analysis, a unit of the New York Structural Biology Center, focused on the structures of proteins residing in biological membranes. Explicit emphasis was placed on currently developing technologies aimed at determining such structures and at understanding their dynamics, mechanisms and complex interactions.

    • Chris Miller
  • Article |

    In vitro assays and high-resolution microscopy show that Pol II CTD undergoes length-dependent liquid phase separation and controls Pol II clustering and mobility in human cells.

    • Marc Boehning
    • , Claire Dugast-Darzacq
    • , Marija Rankovic
    • , Anders S. Hansen
    • , Taekyung Yu
    • , Herve Marie-Nelly
    • , David T. McSwiggen
    • , Goran Kokic
    • , Gina M. Dailey
    • , Patrick Cramer
    • , Xavier Darzacq
    •  & Markus Zweckstetter
  • Article |

    Cryo-EM analyses of human LRRC8A show a homohexameric assembly that can adopt two conformations, compact or relaxed, indicating rigid-body motions that might be involved in channel gating.

    • Go Kasuya
    • , Takanori Nakane
    • , Takeshi Yokoyama
    • , Yanyan Jia
    • , Masato Inoue
    • , Kengo Watanabe
    • , Ryoki Nakamura
    • , Tomohiro Nishizawa
    • , Tsukasa Kusakizako
    • , Akihisa Tsutsumi
    • , Haruaki Yanagisawa
    • , Naoshi Dohmae
    • , Motoyuki Hattori
    • , Hidenori Ichijo
    • , Zhiqiang Yan
    • , Masahide Kikkawa
    • , Mikako Shirouzu
    • , Ryuichiro Ishitani
    •  & Osamu Nureki
  • Article |

    Four crystal structures of the human serotonin receptor 5-HT2BR in complex with chemically and pharmacologically diverse drugs elucidate the structural bases for receptor activation, agonist-mediated biased signaling and β-arrestin2 translocation.

    • John D. McCorvy
    • , Daniel Wacker
    • , Sheng Wang
    • , Bemnat Agegnehu
    • , Jing Liu
    • , Katherine Lansu
    • , Alexandra R. Tribo
    • , Reid H. J. Olsen
    • , Tao Che
    • , Jian Jin
    •  & Bryan L. Roth
  • Article |

    In situ Hi-C and other genome-wide and imaging analyses in different mouse embryonic cell types reveal that the noncanonical SMC protein Smchd1 regulates long-range chromatin interactions and the developmental silencing of Hox genes.

    • Natasha Jansz
    • , Andrew Keniry
    • , Marie Trussart
    • , Heidi Bildsoe
    • , Tamara Beck
    • , Ian D. Tonks
    • , Arne W. Mould
    • , Peter Hickey
    • , Kelsey Breslin
    • , Megan Iminitoff
    • , Matthew E. Ritchie
    • , Edwina McGlinn
    • , Graham F. Kay
    • , James M. Murphy
    •  & Marnie E. Blewitt
  • Article |

    A screen for C. elegans antiviral-defense genes identifies a homolog of the mammalian TUT4(7) terminal uridylyltransferase genes and leads to the discovery of 3′-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.

    • Jérémie Le Pen
    • , Hongbing Jiang
    • , Tomás Di Domenico
    • , Emma Kneuss
    • , Joanna Kosałka
    • , Christian Leung
    • , Marcos Morgan
    • , Christian Much
    • , Konrad L. M. Rudolph
    • , Anton J. Enright
    • , Dónal O’Carroll
    • , David Wang
    •  & Eric A. Miska
  • Article |

    A set of GFP fusions with as few as 12 residues appended to the C terminus is shown to assemble into filaments in E. coli. Crystal structures reveal a mechanism termed ‘runaway domain coupling’ and illustrate how protein filament formation can evolve.

    • Laura McPartland
    • , Danielle M. Heller
    • , David S. Eisenberg
    • , Ann Hochschild
    •  & Michael R. Sawaya
  • Article |

    Time-resolved X-ray crystal structures of RNA hydrolysis by RNase H1 reveal that cations in addition to the two canonical Mg2+ ions position the reactants in the active site and enable catalysis.

    • Nadine L. Samara
    •  & Wei Yang
  • Article |

    Cell-based and in vitro analyses reveal that BRD4 functionally associates with eRNAs and that BRD4 bromodomains, through eRNA interactions, promote BRD4 binding at mutant p53-targeted enhancers to augment enhancer activation and tumor promoting gene expression.

    • Homa Rahnamoun
    • , Jihoon Lee
    • , Zhengxi Sun
    • , Hanbin Lu
    • , Kristen M. Ramsey
    • , Elizabeth A. Komives
    •  & Shannon M. Lauberth
  • Article |

    Cryo-EM structures of the RAG endonuclease in complex with intact DNA substrates reveal that DNA melting is the first step in V(D)J recombination, a mechanism potentially conserved in retroviral integration and DNA transposition.

    • Heng Ru
    • , Wei Mi
    • , Pengfei Zhang
    • , Frederick W. Alt
    • , David G. Schatz
    • , Maofu Liao
    •  & Hao Wu
  • News & Views |

    The effects of RNA secondary structure on translation have been well recognized; however, the global interplay between both in a dynamic cellular system is poorly understood. Beaudoin, Giraldez and colleagues have analyzed RNA structure dynamics during zebrafish embryonic development and have found that the ribosome unzips mRNA secondary structure during translation, thus leading to a global decrease of structure in highly translated transcripts. Furthermore, the authors establish RNA structure in the 3′ untranslated regions of mRNAs as a major regulator of transcript stability in this context.

    • Marianne C. Kramer
    •  & Brian D. Gregory
  • News & Views |

    The mechanism underlying CCG-repeat expansions in patients with fragile X premutation is not well understood. Using a new experimental system in mammalian cells, a study in this issue reports that break-induced replication has a role in CGG-repeat instability.

    • Madhura Deshpande
    •  & Jeannine Gerhardt
  • News & Views |

    A series of new cryo-EM structures reveals a surprising twist in how the RAG complex initiates V(D)J recombination. The initial complex with substrate DNA adopts two conformations: in one, the DNA is relatively undistorted but the scissile phosphate is far from the active site, and in the other the DNA is partially melted and unwound by half a turn, which allows the scissile phosphate to dock into the active site. Similar pre-catalysis DNA melting may occur with other DDE recombinases, for which equivalent complexes with uncleaved substrate DNA are not yet available.

    • Fred Dyda
    •  & Phoebe A. Rice
  • Article |

    The mitochondrial fission dynamin (Dnm1) from an algae is captured in a closed conformation, with the GTPase domain compacted against the stalk. This work indicates that formation of the closed conformation may contribute to membrane fission.

    • Olga Bohuszewicz
    •  & Harry H. Low
  • Article |

    Characterization of mRNA structure during the zebrafish maternal-to-zygotic transition identifies the ribosome as a major RNA structure remodeler in vivo and reveals that structural dynamics can affect gene expression, partly by modulating miRNA activity.

    • Jean-Denis Beaudoin
    • , Eva Maria Novoa
    • , Charles E. Vejnar
    • , Valeria Yartseva
    • , Carter M. Takacs
    • , Manolis Kellis
    •  & Antonio J. Giraldez
  • News & Views |

    Under steady-state conditions, the E3 ubiquitin ligase Parkin is localized to the cytosol in an autoinhibited state. Two recent studies describe the mechanism of Parkin activation by phosphorylation via structural rearrangement of the Ubl and RING2 domains, explaining how the RING2 domain is released from the core of Parkin to allow for ubiquitination of its substrates.

    • François Le Guerroué
    •  & Richard J. Youle