Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly

PLoS Pathogens

Lin-Fa Wang¹  Dimitar B. Nikolov²  Z. Hong Zhou³  Yee-Peng Chan⁴  Lianying Yan⁴  YanRu Feng⁴  Christopher C. Broder⁵  Zeynep Akyol-Ataman⁶  Hector C. Aguilar⁶  Yongqun Zhu⁷  Benhur Lee⁸  Somnath Dutta⁸  Birgit Bradel-Tretheway⁹  Georgios Skiniotis^1,10  Kai Xu^1,11 

[1] CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratory, Geelong, Victoria, Australia;California NanoSystems Institute, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, United States of America;Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, United States of America;Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America;Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America;Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, United States of America;Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China;Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America;Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America;Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore;Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

关键词: Glycoproteins;    Membrane fusion;    Cell fusion;    Virus glycoproteins;    Crystal structure;    Viral entry;    Oligomers;    Host cells;   

DOI  :  10.1371/journal.ppat.1005322

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Nipah virus (NiV) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. The G glycoprotein attaches to cell receptors, triggering the fusion (F) glycoprotein to execute membrane fusion. Here we report the first crystal structure of the pre-fusion form of the NiV-F glycoprotein ectodomain. Interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. Electron tomography of Nipah virus-like particles supported the hexameric pre-fusion model, and biochemical analyses supported the hexamer-of-trimers F assembly in solution. Importantly, structure-assisted site-directed mutagenesis of the interfaces between F trimers highlighted the functional relevance of the hexameric assembly. Shown here, in both cell-cell fusion and virus-cell fusion systems, our results suggested that this hexamer-of-trimers assembly was important during fusion pore formation. We propose that this assembly would stabilize the pre-fusion F conformation prior to cell attachment and facilitate the coordinated transition to a post-fusion conformation of all six F trimers upon triggering of a single trimer. Together, our data reveal a novel and functional pre-fusion architecture of a paramyxoviral fusion glycoprotein.

【 授权许可】

CC BY