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

Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):E2625-34. doi: 10.1073/pnas.1213813109. Epub 2012 Sep 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Cricetinae
  • Crystallography, X-Ray
  • HN Protein / chemistry*
  • HN Protein / genetics
  • HN Protein / metabolism
  • Humans
  • Protein Folding*
  • Protein Structure, Tertiary
  • Rubulavirus / enzymology*
  • Rubulavirus / genetics
  • Vero Cells
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / metabolism
  • Virus Internalization

Substances

  • HN Protein
  • Viral Fusion Proteins