Mutagenesis of paramyxovirus hemagglutinin-neuraminidase membrane-proximal stalk region influences stability, receptor binding, and neuraminidase activity

Emmanuel Adu-Gyamfi, Lori S. Kim, Theodore S. Jardetzky, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Paramyxoviridae consist of a large family of enveloped, negative-sense, nonsegmented single-stranded RNA viruses that account for a significant number of human and animal diseases. The fusion process for nearly all paramyxoviruses involves the mixing of the host cell plasma membrane and the virus envelope in a pH-independent fashion. Fusion is orchestrated via the concerted action of two surface glycoproteins: an attachment protein called hemagglutinin-neuraminidase (HN [also called H or G depending on virus type and substrate]), which acts as a receptor binding protein, and a fusion (F) protein, which undergoes a major irreversible refolding process to merge the two membranes. Recent biochemical evidence suggests that receptor binding by HN is dispensable for cell-cell fusion. However, factors that influence the stability and/or conformation of the HN 4-helix bundle (4HB) stalk have not been studied. Here, we used oxidative cross-linking as well as functional assays to investigate the role of the structurally unresolved membrane-proximal stalk region (MPSR) (residues 37 to 58) of HN in the context of headless and fulllength HN membrane fusion promotion. Our data suggest that the receptor binding head serves to stabilize the stalk to regulate fusion. Moreover, we found that the MPSR of HN modulates receptor binding and neuraminidase activity without a corresponding regulation of F triggering.

Original languageEnglish (US)
Pages (from-to)7778-7788
Number of pages11
JournalJournal of virology
Volume90
Issue number17
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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