title: New insights into the Hendra virus attachment and entry process from structures of the virus G glycoprotein and its complex with Ephrin-B2.
abstract: Hendra virus and Nipah virus, comprising the genus Henipavirus, are recently emerged, highly pathogenic and often lethal zoonotic agents against which there are no approved therapeutics. Two surface glycoproteins, the attachment (G) and fusion (F), mediate host cell entry. The crystal structures of the Hendra G glycoprotein alone and in complex with the ephrin-B2 receptor reveal that henipavirus uses Tryptophan 122 on ephrin-B2/B3 as a "latch" to facilitate the G-receptor association. Structural-based mutagenesis of residues in the Hendra G glycoprotein at the receptor binding interface document their importance for viral attachments and entry, and suggest that the stability of the Hendra-G-ephrin attachment complex does not strongly correlate with the efficiency of viral entry. In addition, our data indicates that conformational rearrangements of the G glycoprotein head domain upon receptor binding may be the trigger leading to the activation of the viral F fusion glycoprotein during virus infection.
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.forename: Yee-Peng
authors.initials: YP
authors.lastname: Chan
authors.forename: Kanagalaghatta R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: Dimple
authors.initials: D
authors.lastname: Khetawat
authors.forename: Lianying
authors.initials: L
authors.lastname: Yan
authors.forename: Momchil V
authors.initials: MV
authors.lastname: Kolev
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Nikolov
mesh_terms: D018360:Crystallography, X-Ray; D036388:Ephrin-B2 / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D045404:Hendra Virus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D036388:Ephrin-B2; D006023:Glycoproteins; D011991:Receptors, Virus; D014764:Viral Proteins