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

Department of Molecular Biosciences and Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2012; 109(39):E2625-34. DOI: 10.1073/pnas.1213813109
Source: PubMed


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.

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    • "This back-folded organization may preclude productive lateral interaction with prefusion F trimers. Consequently, Yuan and colleagues speculated that upon receptor binding, the two dimers move into a “heads-up” position, which uncovers the F interaction sites in the HN stalk region and facilitates HN/F interactions (51). Consistent with this model, HN-type paramyxovirus attachment proteins are thought not to interact with F trimers in the secretory system of the host cell and typically do not coprecipitate with F (52). "
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