TY - JOUR
T1 - Fusion activation by a headless parainfluenza virus 5 hemagglutinin- neuraminidase stalk suggests a modular mechanism for triggering
AU - Bose, Sayantan
AU - Zokarkar, Aarohi
AU - Welch, Brett D.
AU - Leser, George P.
AU - Jardetzky, Theodore S.
AU - Lamb, Robert A.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/9/25
Y1 - 2012/9/25
N2 - 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.
AB - 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.
KW - Fusion triggering
KW - Hemagglutinin-neuraminidase structure
KW - Protein refolding
KW - Viral membrane fusion
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U2 - 10.1073/pnas.1213813109
DO - 10.1073/pnas.1213813109
M3 - Article
C2 - 22949640
AN - SCOPUS:84866859065
VL - 109
SP - E2625-E2634
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 39
ER -