Structural biology

  • Article |

    Cryo-electron microscopy studies show that dynamic coordination of Na+ in the ion channel of Dispatched homologue 1 and the transmembrane Na+ gradient have key roles in exporting lipid-modified Hedgehog protein signal.

    • Qianqian Wang
    • , Daniel E. Asarnow
    •  & Philip A. Beachy
  • Article
    | Open Access

    Cryo-EM structure of Nf1 protein is reported, revealing closed and open conformations that regulate interaction with Ras oncogene, setting the stage for understanding the mechanistic action of Nf1 and how disease mutations lead to dysfunction.

    • Andreas Naschberger
    • , Rozbeh Baradaran
    •  & Marta Carroni
  • Article |

    The cryo-electron microscopy structure of domain 1 of the LDLRAD3 receptor in complex with virus-like particles of Venezuelan equine encephalitis virus (VEEV) provides insights into the assembly and entry of VEEV and other alphaviruses.

    • Bingting Ma
    • , Cuiqing Huang
    •  & Xinzheng Zhang
  • Article |

    Structural studies of the complex of anaplastic lymphoma kinase and leukocyte tyrosine kinase and their activating cytokines identify unique architectural features of the complex, and provide a novel mechanistic paradigm among receptor tyrosine kinases.

    • Steven De Munck
    • , Mathias Provost
    •  & Savvas N. Savvides
  • Article
    | Open Access

    Structure of human nuclear pore complex in its cellular environment reveals a substantially dilated central channel and shows that its nucleoplasmic and cytoplasmic rings restrict channel dimensions and create membrane asymmetry at the inner ring.

    • Anthony P. Schuller
    • , Matthias Wojtynek
    •  & Thomas U. Schwartz
  • Article |

    Cryo-electron microscopy structures of tau filaments from progressive supranuclear palsy and other tauopathies reveal new filament conformations, and suggest that tauopathies can be classified on several different levels according to their filament folds.

    • Yang Shi
    • , Wenjuan Zhang
    •  & Sjors H. W. Scheres
  • Article
    | Open Access

    Cryo-electron microscopy structures of the voltage-gated potassium channel Kv4.2 alone and in complex with auxiliary subunits (DPP6S and/or KChIP1) reveal the distinct mechanisms of these two different subunits in modulating channel activity.

    • Yoshiaki Kise
    • , Go Kasuya
    •  & Osamu Nureki
  • Article |

    Cryo-electron microscopy structures of the luteinizing hormone–choriogonadotropin receptor (LHCGR), in complex with Gs and in various states of activation, reveal a distinct mechanism of receptor activation, with implications for drug discovery.

    • Jia Duan
    • , Peiyu Xu
    •  & H. Eric Xu
  • Article |

    The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.

    • Lingli He
    • , Jiahui Sun
    •  & Yan Zhao
  • Article
    | Open Access

    The authors resolve the structure of five complexes containing RNA polymerase II and the CSA and CSB proteins, offering insight into how the repair of DNA lesions is coupled to transcription.

    • Goran Kokic
    • , Felix R. Wagner
    •  & Patrick Cramer
  • Article |

    Crystal structures of the hepatitis C virus (HCV) glycoprotein E2 in complex with CD81 reveal the conformational changes that occur in E2 after binding of CD81 and the effects of pH on binding affinity.

    • Ashish Kumar
    • , Reafa A. Hossain
    •  & Joseph Marcotrigiano
  • Article |

    MIPS521, a positive allosteric modulator of the adenosine A1 receptor, has analgesic properties in a rat model of neuropathic pain through a mechanism by which MIPS521 stabilizes the complex between adenosine, receptor and G protein.

    • Christopher J. Draper-Joyce
    • , Rebecca Bhola
    •  & Arthur Christopoulos
  • Article |

    Structural, functional and localization studies reveal that Geobacter sulfurreducens pili cannot behave as microbial nanowires, instead functioning in a similar way to secretion pseudopili to export cytochrome nanowires that are essential for extracellular electron transfer.

    • Yangqi Gu
    • , Vishok Srikanth
    •  & Nikhil S. Malvankar
  • Article |

    Cryo-electron microscopy structures of a PIWI–piRNA complex provide insight into how piRNAs recognise target RNAs and reveal differences from the target mechanisms of microRNAs.

    • Todd A. Anzelon
    • , Saikat Chowdhury
    •  & Ian J. MacRae
  • Article |

    Structural and mechanistic data of the ADP-ribosyltransferase DarT demonstrate the role of ADP-ribosylation of DNA by this enzyme in generating toxicity and regulating cellular signalling processes in bacteria.

    • Marion Schuller
    • , Rachel E. Butler
    •  & Ivan Ahel
  • Article
    | Open Access

    The cryo-electron microscopy structure of a newly identified, early spliceosomal complex reveals the mechanism by which the RNA helicase Prp5 enhances the fidelity of the excision of introns from precursor mRNAs.

    • Zhenwei Zhang
    • , Norbert Rigo
    •  & Reinhard Lührmann
  • Article
    | Open Access

    AlphaFold is used to predict the structures of almost all of the proteins in the human proteome—the availability of high-confidence predicted structures could enable new avenues of investigation from a structural perspective.

    • Kathryn Tunyasuvunakool
    • , Jonas Adler
    •  & Demis Hassabis
  • Article |

    The human monoclonal antibody S2X259 cross-reacts with spike proteins from all clades of sarbecovirus, and provides prophylactic and therapeutic protection in vivo against parental SARS-CoV-2 and emerging variants of concern.

    • M. Alejandra Tortorici
    • , Nadine Czudnochowski
    •  & Matteo Samuele Pizzuto
  • Article
    | Open Access

    AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

    • John Jumper
    • , Richard Evans
    •  & Demis Hassabis
  • Article |

    Cryo-electron microscopy structures of human Cav2.2 in the presence or absence of ziconotide reveal the molecular basis of the specificity of this painkiller for Cav2.2, and provide insights into electromechanical coupling in Cav channels.

    • Shuai Gao
    • , Xia Yao
    •  & Nieng Yan
  • Article |

    A structure of the sperm-specific CatSper complex features a number of additional components; together, these components and the CatSper complex are termed the CatSpermasome.

    • Shiyi Lin
    • , Meng Ke
    •  & Jianping Wu
  • Article |

    Cryo-electron microscopy structures show that metabotropic glutamate receptor 2 forms a dimer to which only one G protein is coupled, revealing the basis for asymmetric signal transduction.

    • Alpay B. Seven
    • , Ximena Barros-Álvarez
    •  & Georgios Skiniotis
  • Article |

    Cryo-EM structures of human calcium-sensing receptor reveal intrinsic asymmetry in the receptor homodimer upon activation that is stabilized by calcimimetic drugs adopting distinct poses in the two protomers, priming one protomer for G-protein coupling.

    • Yang Gao
    • , Michael J. Robertson
    •  & Georgios Skiniotis
  • Article |

    Cryo-electron microscopy structures of homo- and heterodimers of mGlu2 and mGlu7 provide insights into their dimerization modes and the subunit conformational changes that characterize the activation of these class C G-protein-coupled receptors.

    • Juan Du
    • , Dejian Wang
    •  & Qiang Zhao
  • Article |

    Cryo-electron microscopy structures of PCFT in a substrate-free state and bound to the antifolate drug pemetrexed provide insights into how this protein recognizes folates and mediates their transport into cells.

    • Joanne L. Parker
    • , Justin C. Deme
    •  & Simon Newstead
  • Article
    | Open Access

    A cryo-electron microscopy structure of the inner membrane complex of the ESX-5 type VII secretion system of Mycobacterium tuberculosis reveals an important role of interactions with MycP5 protease for complex integrity.

    • Catalin M. Bunduc
    • , Dirk Fahrenkamp
    •  & Thomas C. Marlovits