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  • Article |

    Cryo-EM structures of Escherichia coli ClpAP undergoing active substrate unfolding and proteolysis reveal contacts that drive substrate translocation and a dynamic switch mechanism at the ClpA–ClpP interface.

    • Kyle E. Lopez
    • , Alexandrea N. Rizo
    • , Eric Tse
    • , JiaBei Lin
    • , Nathaniel W. Scull
    • , Aye C. Thwin
    • , Aaron L. Lucius
    • , James Shorter
    •  & Daniel R. Southworth

  • Article |

    A cryo-EM structure of a stable, protease-resistant fibril formed by a fragment of the human prion protein shows two intertwined protofilaments with a tightly packed hydrophobic interface.

    • Calina Glynn
    • , Michael R. Sawaya
    • , Peng Ge
    • , Marcus Gallagher-Jones
    • , Connor W. Short
    • , Ronquiajah Bowman
    • , Marcin Apostol
    • , Z. Hong Zhou
    • , David S. Eisenberg
    •  & Jose A. Rodriguez

  • Editorial |

    Initiatives to promote transparency in our peer-review process and reproducibility start to take off.

  • Brief Communication |

    The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the unique details of SALL4 recruitment, providing insights for rational design of cereblon-binding drugs with reduced teratogenic risk.

    • Mary E. Matyskiela
    • , Thomas Clayton
    • , Xinde Zheng
    • , Christopher Mayne
    • , Eileen Tran
    • , Aaron Carpenter
    • , Barbra Pagarigan
    • , Joseph McDonald
    • , Mark Rolfe
    • , Lawrence G. Hamann
    • , Gang Lu
    •  & Philip P. Chamberlain

  • Article |

    Cryo-EM structures of human ESCRT-III proteins forming membrane-bound and membrane-free filaments show how CHMP1B and IST1 polymerize sequentially, driving membrane tubulation, constriction and bilayer thinning, leading to membrane fission.

    • Henry C. Nguyen
    • , Nathaniel Talledge
    • , John McCullough
    • , Abhimanyu Sharma
    • , Frank R. Moss III
    • , Janet H. Iwasa
    • , Michael D. Vershinin
    • , Wesley I. Sundquist
    •  & Adam Frost

  • Article |

    Cryo-EM structures of the bovine bestrophin-2 (Best2) channel, in the presence and absence of Ca2+, reveal the differences between bestrophin paralogs, the structural basis for the ion selectivity of bovine Best2 and its Ca2+-independent activity for Cl−.

    • Aaron P. Owji
    • , Qingqing Zhao
    • , Changyi Ji
    • , Alec Kittredge
    • , Austin Hopiavuori
    • , Ziao Fu
    • , Nancy Ward
    • , Oliver B. Clarke
    • , Yin Shen
    • , Yu Zhang
    • , Wayne A. Hendrickson
    •  & Tingting Yang

  • Perspective |

    Emerging evidence that telomere-specific Shelterin components also play roles in DNA replication timing within heterochromatin and genome maintenance suggests a potential common evolutionary origin of their protective and regulatory functions.

    • Aaron Mendez-Bermudez
    • , Marie-Josèphe Giraud-Panis
    • , Jing Ye
    •  & Eric Gilson

  • News & Views |

    Poly-(ADP-ribosylation) is a post-translational modification with broad roles in cell signaling. A recently reported crystal structure reveals how the accessory factor HPF1 extends the catalytic active site of PARP1 and PARP2 to promote the specific ADP-ribosylation of serine residues, a prerequisite for dynamic chromatin changes induced by DNA damage.

    • Charlotte Blessing
    •  & Andreas G. Ladurner

  • Article |

    The chaperone Hsp27 prevents FUS from undergoing liquid–liquid phase separation until stress-induced phosphorylation causes Hsp27 to partition with FUS to preserve the liquid phase against amyloid fibril formation.

    • Zhenying Liu
    • , Shengnan Zhang
    • , Jinge Gu
    • , Yilun Tong
    • , Yichen Li
    • , Xinrui Gui
    • , Houfang Long
    • , Chuchu Wang
    • , Chunyu Zhao
    • , Jinxia Lu
    • , Lin He
    • , Ying Li
    • , Zhijun Liu
    • , Dan Li
    •  & Cong Liu

  • Article |

    Cryo-EM structures of plasma membrane ATP release channel pannexin 1 reveal heptameric architecture, wide pore and a constriction potentially restricting the size of permeable substrates. Combined with functional assays, they offer insights into channel gating.

    • Zengqin Deng
    • , Zhihui He
    • , Grigory Maksaev
    • , Ryan M. Bitter
    • , Michael Rau
    • , James A. J. Fitzpatrick
    •  & Peng Yuan

  • News & Views |

    Adenosine deaminases acting on RNA (ADARs) catalyze deamination of adenosine to inosine. irCLASH identifies dsRNA substrates of ADARs and defines new features of their RNA-binding and editing activity, improving our understanding of these enzymes and aiding with future therapeutic applications.

    • Riccardo Pecori
    •  & Nina F. Papavasiliou

  • Article |

    Circular nanoparticles self-assembled from designed tandem repeat proteins are functionalized by fusing different protein domains at defined positions and copy numbers. These constructs can activate T cells via high-avidity interactions on the cell surface.

    • Colin E. Correnti
    • , Jazmine P. Hallinan
    • , Lindsey A. Doyle
    • , Raymond O. Ruff
    • , Carla A. Jaeger-Ruckstuhl
    • , Yuexin Xu
    • , Betty W. Shen
    • , Amanda Qu
    • , Caley Polkinghorn
    • , Della J. Friend
    • , Ashok D. Bandaranayake
    • , Stanley R. Riddell
    • , Brett K. Kaiser
    • , Barry L. Stoddard
    •  & Philip Bradley

  • Article |

    Transcriptome-wide mapping of RNAs bound by human ADARs reveals features that determine ADAR binding affinity and editing efficiency.

    • Yulong Song
    • , Wenbing Yang
    • , Qiang Fu
    • , Liang Wu
    • , Xueni Zhao
    • , Yusen Zhang
    •  & Rui Zhang

  • Article |

    Identification of SDD1 mRNA from Saccharomyces cerevisiae as an endogenous RQC substrate allows analysis of the mechanism underlying translational stalling and Hel2-dependent polyubiquitination of collided ribosomes to provide insight into ribosome dissociation.

    • Yoshitaka Matsuo
    • , Petr Tesina
    • , Shizuka Nakajima
    • , Masato Mizuno
    • , Akinori Endo
    • , Robert Buschauer
    • , Jingdong Cheng
    • , Okuto Shounai
    • , Ken Ikeuchi
    • , Yasushi Saeki
    • , Thomas Becker
    • , Roland Beckmann
    •  & Toshifumi Inada

  • Article |

    A combination of cellular, in vitro phase separation and functional assays shows that the intrinsically disordered regions and bromodomains of the BRD4 short isoform induce formation of liquid-like condensates in cancer cell nuclei and enhance transcriptional activity.

    • Xinye Han
    • , Di Yu
    • , Ruirui Gu
    • , Yanjie Jia
    • , Qi Wang
    • , Anbalagan Jaganathan
    • , Xuelan Yang
    • , Miaomiao Yu
    • , Nicolas Babault
    • , Chengcheng Zhao
    • , Huanfa Yi
    • , Qiang Zhang
    • , Ming-Ming Zhou
    •  & Lei Zeng

  • Article |

    Using computational, spectroscopic and in vivo approaches, two short motifs in the N-terminal region of human α-synuclein are shown to be critical for toxic protein aggregation but also for membrane fusion.

    • Ciaran P. A. Doherty
    • , Sabine M. Ulamec
    • , Roberto Maya-Martinez
    • , Sarah C. Good
    • , Jemma Makepeace
    • , G. Nasir Khan
    • , Patricija van Oosten-Hawle
    • , Sheena E. Radford
    •  & David J. Brockwell

  • Article |

    Cryo-EM structure of the human PAC1R receptor bound to its neuropeptide ligand PACAP and to an engineered Gs complex reveals the mode of PACAP recognition and suggests functional diversity of the extracellular domains in class B GPCRs.

    • Kazuhiro Kobayashi
    • , Wataru Shihoya
    • , Tomohiro Nishizawa
    • , Francois Marie Ngako Kadji
    • , Junken Aoki
    • , Asuka Inoue
    •  & Osamu Nureki

  • Article |

    The RNA-binding protein SRSF7 autoregulates its protein levels through an intricate negative feedback mechanism that involves translation of two distinct protein halves, termed Split-ORFs; the potential to encode Split-ORFs is also seen in other targets of nonsense-mediated decay.

    • Vanessa Königs
    • , Camila de Oliveira Freitas Machado
    • , Benjamin Arnold
    • , Nicole Blümel
    • , Anfisa Solovyeva
    • , Sinah Löbbert
    • , Michal Schafranek
    • , Igor Ruiz De Los Mozos
    • , Ilka Wittig
    • , Francois McNicoll
    • , Marcel H. Schulz
    •  & Michaela Müller-McNicoll

  • Article |

    Structural and binding studies show that a repeated peptide motif in the N-terminal domain of CsoS2 mediates multivalent interactions with assembled Rubisco to facilitate its encapsulation into the carboxysome.

    • Luke M. Oltrogge
    • , Thawatchai Chaijarasphong
    • , Allen W. Chen
    • , Eric R. Bolin
    • , Susan Marqusee
    •  & David F. Savage

  • News & Views |

    Recent studies report the first structures of two CALHM family members, describing unexpected oligomeric architecture and providing insights into the mechanism of function of CALHM channels.

    • J. Kevin Foskett

  • News & Views |

    Many AAA+ ATPases assemble as hexamers to unfold protein substrates using a hand-over-hand, threading mechanism, but the Bcs1 AAA+ ATPase facilitates mitochondrial membrane translocation of the folded iron–sulfur Rieske protein. Two reports reveal that Bcs1 adopts an unusual heptameric configuration and provide insights into a non-canonical translocation mechanism.

    • Peter S. Shen

  • Brief Communication |

    A 3.3-Å-resolution cryo-EM structure of yeast Maf1 bound to RNA polymerase III (Pol III) explains the molecular mechanism for Pol III inhibition.

    • Matthias K. Vorländer
    • , Florence Baudin
    • , Robyn D. Moir
    • , René Wetzel
    • , Wim J. H. Hagen
    • , Ian M. Willis
    •  & Christoph W. Müller

  • Article |

    Whole-genome siRNA screens to identify regulators of human LINE-1 retrotransposition reveal that BRCA1 and Fanconi anemia DNA repair factors inhibit retrotransposition at stalled replication fork targets created and exploited by L1.

    • Paolo Mita
    • , Xiaoji Sun
    • , David Fenyö
    • , David J. Kahler
    • , Donghui Li
    • , Neta Agmon
    • , Aleksandra Wudzinska
    • , Sarah Keegan
    • , Joel S. Bader
    • , Chi Yun
    •  & Jef D. Boeke

  • Article |

    Knockout screens to assess the effect of LINE-1 expression on cell growth show that TP53-deficient cells require replication-stress signaling and replication-fork restart factors to suppress LINE-1 toxicity, and that LINE-1 expression activates the Fanconi anemia pathway, suggesting that retrotransposition conflicts with DNA replication.

    • Daniel Ardeljan
    • , Jared P. Steranka
    • , Chunhong Liu
    • , Zhi Li
    • , Martin S. Taylor
    • , Lindsay M. Payer
    • , Mikhail Gorbounov
    • , Jacob S. Sarnecki
    • , Vikram Deshpande
    • , Ralph H. Hruban
    • , Jef D. Boeke
    • , David Fenyö
    • , Pei-Hsun Wu
    • , Agata Smogorzewska
    • , Andrew J. Holland
    •  & Kathleen H. Burns

  • Article |

    Mutations in cysteine string protein-α (CSPα) cause its aggregation and adult-onset neuronal ceroid lipofuscinosis. Abnormal binding of Fe–S clusters to CSPα mutants is now implicated in driving aggregation, which can be reversed in neurons by clinically approved iron chelators.

    • Nima N. Naseri
    • , Burçe Ergel
    • , Parinati Kharel
    • , Yoonmi Na
    • , Qingqiu Huang
    • , Rong Huang
    • , Natalia Dolzhanskaya
    • , Jacqueline Burré
    • , Milen T. Velinov
    •  & Manu Sharma

  • Article |

    Cryo-EM structures of nick forming complexes of the mouse RAG recombinase with DNA substrates demonstrate how the RAG active site is reconfigured for two consecutive DNA cleavage reactions.

    • Xuemin Chen
    • , Yanxiang Cui
    • , Robert B. Best
    • , Huaibin Wang
    • , Z. Hong Zhou
    • , Wei Yang
    •  & Martin Gellert

  • Resource |

    NEDD8-ubiquitin substrate profiling (sNUSP) identifies neddylation sites in many non-cullin proteins. Among the candidates, neddylation of cofilin regulates actin dynamics and neurite growth and outgrowth in developing neurons.

    • Annette M. Vogl
    • , Lilian Phu
    • , Raquel Becerra
    • , Sebastian A. Giusti
    • , Erik Verschueren
    • , Trent B. Hinkle
    • , Martín D. Bordenave
    • , Max Adrian
    • , Amy Heidersbach
    • , Patricio Yankilevich
    • , Fernando D. Stefani
    • , Wolfgang Wurst
    • , Casper C. Hoogenraad
    • , Donald S. Kirkpatrick
    • , Damian Refojo
    •  & Morgan Sheng

  • Article |

    Structural elucidation of the RAG strand transfer complex reveals how the recombinase efficiently catalyzes both forward and reverse integration reactions to prevent RAG-mediated transposition events.

    • Xuemin Chen
    • , Yanxiang Cui
    • , Huaibin Wang
    • , Z. Hong Zhou
    • , Martin Gellert
    •  & Wei Yang

  • Comment |

    A symposium to remember the life of Raj Rajashankar and to highlight the many scientific achievements to which he contributed was also an occasion to reflect on the fundamental role of personal interactions in the research enterprise.

    • Filippo Mancia
    •  & Stephen C. Harrison

  • Article |

    Crystal structures of human BRAF kinase domain with MEK and an ATP analog or with 14-3-3 reveal how ATP exerts a negative regulatory effect on the kinase and how this effect is relieved by dimeric 14-3-3.

    • Nicholas P. D. Liau
    • , Timothy J. Wendorff
    • , John G. Quinn
    • , Micah Steffek
    • , Wilson Phung
    • , Peter Liu
    • , Jia Tang
    • , Flaviyan J. Irudayanathan
    • , Saeed Izadi
    • , Andrey S. Shaw
    • , Shiva Malek
    • , Sarah G. Hymowitz
    •  & Jawahar Sudhamsu

  • Article |

    Cryo-EM structures of the calcium homeostasis modulator channels chicken CALHM1 and human CALHM2 reveal that they function as octa- and undecamers, respectively. Molecular dynamics simulations suggest that a lipid bilayer can form within the CALHM2 pore.

    • Johanna L. Syrjanen
    • , Kevin Michalski
    • , Tsung-Han Chou
    • , Timothy Grant
    • , Shanlin Rao
    • , Noriko Simorowski
    • , Stephen J. Tucker
    • , Nikolaus Grigorieff
    •  & Hiro Furukawa