Class II Membrane Fusion Proteins in Viral and Cellular Fusion Events

Abstract

Class II proteins are viral membrane fusogenic molecules folded essentially as beta-sheet and having an internal fusion peptide. In particular, they lack the characteristic central alpha-helical coiled coil present in the post-fusion conformation of all other viral fusion proteins. The regular, symmetric enveloped viruses that have been studied so far, such as flaviviruses and alphaviruses, have been shown to have class II fusion proteins, which in their pre-fusion conformation make an icosahedral shell surrounding the viral membrane. The negative-stranded RNA viruses of the bunyavirus family - which have been shown to display a regular icosahedral glycoprotein shell at their surface, have also been predicted to have class II fusion proteins. We have recently identified the rubella virus fusion protein as class II, although the virus particles appear pleomorphic. In spite of the lack of sequence conservation, the available structures indicate that class II proteins have evolved from a distal, ancestral gene. We have now discovered that the cellular fusion protein Eff-1, involved in syncytium formation during the genesis of the skin in nematodes (C. elegans) and in other multicellular organisms, are also folded as a class II viral fusion proteins, thereby indicating common ancestry. My talk will discuss the implications of this finding, which highlights the intricate exchange of genetic information that have taken place between viruses and cells during evolution. It also suggest a mechanism for the cell-cell fusion process, which ahs not been studied so far.