Fusion activation by a headless parainfluenza virus 5 hemagglutinin- neuraminidase stalk suggests a modular mechanism for triggering

Sayantan Bose, Aarohi Zokarkar, Brett D. Welch, George P. Leser, Theodore S. Jardetzky, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticle

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E2625-E2634
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number39
DOIs
StatePublished - Sep 25 2012

Keywords

  • Fusion triggering
  • Hemagglutinin-neuraminidase structure
  • Protein refolding
  • Viral membrane fusion

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Fusion activation by a headless parainfluenza virus 5 hemagglutinin- neuraminidase stalk suggests a modular mechanism for triggering'. Together they form a unique fingerprint.

  • Cite this