title: Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly.
abstract: 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.
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.
authors.forename: Yee-Peng
authors.initials: YP
authors.lastname: Chan
authors.affiliation: Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America.
authors.forename: Birgit
authors.initials: B
authors.lastname: Bradel-Tretheway
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, United States of America.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Akyol-Ataman
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yongqun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Somnath
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.
authors.forename: Lianying
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.
authors.forename: YanRu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratory, Geelong, Victoria, Australia.|Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America.|Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Georgios
authors.initials: G
authors.lastname: Skiniotis
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Benhur
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, United States of America.|California NanoSystems Institute, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, United States of America.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
authors.affiliation: Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America.
authors.forename: Hector C
authors.initials: HC
authors.lastname: Aguilar
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Nikolov
mesh_terms: D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D057809:HEK293 Cells; D045464:Henipavirus Infections / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D045405:Nipah Virus / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D053586:Virus Internalization
chemical_list: C510755:F protein, Nipah virus; D014759:Viral Envelope Proteins