Peptides and membrane fusion: Towards an understanding of the molecular mechanism of protein-induced fusion

Processes such as endo- or exocytosis, membrane recycling, fertilization an d enveloped viruses infection require one or more critical membrane fusion reactions. A key feature in viral and cellular fusion phenomena is the invo lvement of specific fusion proteins. Among the few well-characterized fusio n proteins are Viral spike glycoproteins responsible for penetration of env eloped viruses into their host cells, and sperm proteins involved in sperm- egg fusion. In their sequences, these proteins possess a "fusion peptide," a short segment (up to 20 amino acids) of relatively hydrophobic residues, commonly found in a membrane-anchored polypeptide chain. To simulate protei n-mediated fusion, many studies on peptide-induced membrane fusion have bee n conducted on model membranes such as liposomes and have employed syntheti c peptides corresponding to the putative fusion sequences of viral proteins , or de novo synthesized peptides. Here, the application of peptides as a m odel system to understand the molecular details of membrane fusion will be discussed in detail. Data obtained from these studies will be correlated to biological studies, in particular those that involve viral and sperm-egg s ystems. Structure-function relationships will be revealed, particularly in the context of protein-induced membrane perturbations and bilayer-to-nonbil ayer transition underlying the mechanism of fusion. We will also focus on t he involvement of Lipid composition of membranes as a potential regulating factor of the topological fusion site in biological systems.