Functional domains within fusion proteins: prospectives for development of peptide inhibitors of viral cell fusion.

Abstract

The entry of enveloped viruses into host cells is accomplished by fusion of the viral envelope and target plasma membrane and is mediated by fusion proteins. Recently, several functional domains within fusion proteins from different viral families were identified. Some are directly involved in conformational changes after receptor binding, as suggested by the recent release of crystallographically determined structures of a highly stable core structure of the fusion proteins in the absence of membranes. However, in the presence of membranes, this core binds strongly to the membrane's surface and dissociates therein. Other regions, besides the N-terminal fusion peptide, which include the core region and an internal fusion peptide in paramyxoviruses, are directly involved in the actual membrane fusion event, suggesting an "umbrella" like model for the membrane induced conformational change of fusion proteins. Peptides resembling these regions have been shown to have specific antiviral activity, presumably because they interfere with the corresponding domains within the viruses. Overall, these studies shed light into the molecular mechanism of membrane fusion induced by envelope glycoproteins and suggest that fusion proteins from different viral families share common structural and functional motifs.