Fusion activation through attachment protein stalk domains indicates a conserved core mechanism of paramyxovirus entry into cells

Sayantan Bose, Albert S. Song, Theodore S. Jardetzky, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Paramyxoviruses are a large family of membrane-enveloped negative-stranded RNA viruses causing important diseases in humans and animals. Two viral integral membrane glycoproteins (fusion [F] and attachment [HN, H, or G]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. However, the sequence of events that closely links the timing of receptor recognition by HN, H, or G and the "triggering" interaction of the attachment protein with F is unclear. F activation results in F undergoing a series of irreversible conformational rearrangements to bring about membrane merger and virus entry. By extensive study of properties of multiple paramyxovirus HN proteins, we show that key features of F activation, including the F-activating regions of HN proteins, flexibility within this F-activating region, and changes in globular head-stalk interactions are highly conserved. These results, together with functionally active "headless" mumps and Newcastle disease virus HN proteins, provide insights into the F-triggering process. Based on these data and very recently published data for morbillivirus H and henipavirus G proteins, we extend our recently proposed "stalk exposure model" to other paramyxoviruses and propose an "induced fit" hypothesis for F-HN/H/G interactions as conserved core mechanisms of paramyxovirus-mediated membrane fusion.

Original languageEnglish (US)
Pages (from-to)3925-3941
Number of pages17
JournalJournal of virology
Volume88
Issue number8
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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