Abstract
Enveloped viruses always gain entry into the cytoplasm by fusion of their lipid envelope with a cell membrane. Some enveloped viruses fuse directly with the host cell plasma membrane after virus binding to the cell receptor. Other enveloped viruses enter the cells by the endocytic pathway, and fusion depends on the acidification of the endosomal compartment. In both cases, virus-induced membrane fusion is triggered by conformational changes in viral envelope glycoproteins. Two different classes of viral fusion proteins have been described on the basis of their molecular architecture. Several structural data permitted the elucidation of the mechanisms of membrane fusion mediated by class I and class II fusion proteins. In this article, we review a number of results obtained by our laboratory and by others that suggest that the mechanisms involved in rhabdovirus fusion are different from those used by the two well-studied classes of viral glycoproteins. We focus our discussion on the electrostatic nature of virus binding and interaction with membranes, especially through phosphatidylserine, and on the reversibility of the conformational changes of the rhabdovirus glycoprotein involved in fusion. Taken together, these data suggest the existence of a third class of fusion proteins and support the idea that new insights should emerge from studies of membrane fusion mediated by the G protein of rhabdoviruses. In particular, the elucidation of the three-dimensional structure of the G protein or even of the fusion peptide at different pH's might provide valuable information for understanding the fusion mechanism of this new class of fusion proteins.
Highlights
The plasma membrane of eukaryotic cells serves as a barrier against invading parasites and viruses
We review a number of results obtained by our laboratory and by others that suggest that the mechanisms involved in rhabdovirus fusion are different from those used by the two well-studied classes of viral glycoproteins
We focus our discussion on the electrostatic nature of virus binding and interaction with membranes, especially through phosphatidylserine, and on the reversibility of the conformational changes of the rhabdovirus glycoprotein involved in fusion
Summary
The viral fusion glycoproteins share a number of common features: a) they are type I integral membrane proteins presenting a large ectodomain, a single transmembrane sequence and a small C-terminal end inside the viral membrane; b) they contain an Nterminal signal sequence that is cleaved after directing the protein at the endoplasmic reticulum; c) they contain N-linked carbohydrates; d) they form oligomers and occur at high density in the viral membrane; e) they contain a specific segment involved in membrane fusion known as the fusion peptide. The acidic pH of the endosome induces a disassembly of envelope protein dimers, which rearrange in trimers with the fusion peptide loops clustered at one end of an elongated molecule Despite their structural differences, both class I and class II fusion proteins are synthesized in a metastable conformation, and it is believed that the irreversible transition to the post-fusion state provides the energy for membrane fusion.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Brazilian Journal of Medical and Biological Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.