title: Fusion activation by a headless parainfluenza virus 5 hemagglutinin-neuraminidase stalk suggests a modular mechanism for triggering.
abstract: The Paramyxoviridae family of enveloped viruses enters cells through the concerted action of two viral glycoproteins. The receptor-binding protein, hemagglutinin-neuraminidase (HN), H, or G, binds its cellular receptor and activates the fusion protein, F, which, through an extensive refolding event, brings viral and cellular membranes together, mediating virus-cell fusion. However, the underlying mechanism of F activation on receptor engagement remains unclear. Current hypotheses propose conformational changes in HN, H, or G propagating from the receptor-binding site in the HN, H, or G globular head to the F-interacting stalk region. We provide evidence that the receptor-binding globular head domain of the paramyxovirus parainfluenza virus 5 HN protein is entirely dispensable for F activation. Considering together the crystal structures of HN from different paramyxoviruses, varying energy requirements for fusion activation, F activation involving the parainfluenza virus 5 HN stalk domain, and properties of a chimeric paramyxovirus HN protein, we propose a simple model for the activation of paramyxovirus fusion.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Bose
authors.forename: Aarohi
authors.initials: A
authors.lastname: Zokarkar
authors.forename: Brett D
authors.initials: BD
authors.lastname: Welch
authors.forename: George P
authors.initials: GP
authors.lastname: Leser
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Jardetzky
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D006224:Cricetinae; D018360:Crystallography, X-Ray; D015707:HN Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D019213:Rubulavirus / Q000201:enzymology* / Q000235:genetics; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D015707:HN Protein; D014760:Viral Fusion Proteins