Class III Viral Membrane Fusion Proteins

Members of class III of viral fusion proteins share common structural features and molecular architecture, although they belong to evolutionary distant viruses and carry no sequence homology. Based of the experimentally determined three-dimensional structures of their ectodomains, glycoprotein B (gB) of herpesviruses, G protein of rhabdoviruses and glycoprotein 64 (gp64) of baculoviruses have been identified as class III fusion proteins. The structures are proposed to represent post-fusion conformations, and they reveal trimeric, elongated, rod-like molecules, with each protomer being composed of five domains. Sequences which interact with target membranes and form the fusion peptides are located in two loops found at one end of the molecule. Class III fusion proteins are embedded in viral envelope with the principal function of catalyzing fusion of viral and cellular membranes, an event that is essential for infection to occur. In addition, they have been implicated in processes such as attachment to target cells and viral maturation. G protein is the only class III fusion protein for which structures of both pre- and post-fusion states have been determined, shedding light on the mechanism involved in the conformational change and membrane fusion. Whether similar structural organization of class III fusion proteins translates into a common mechanism involved in carrying out membrane fusion remains to be investigated.