Common properties of fusion peptides from diverse systems.

Although membrane fusion occurs ubiquitously and continuously in all eukaroytic cells, little is known about the mechanism that governs lipid bilayer fusion associated with any intracellular fusion reactions. Recent studies of the fusion of enveloped viruses with host cell membranes have helped to define the fusion process. The identification and characterization of key proteins involved in fusion reactions have mainly driven recent advances in our understanding of membrane fusion. The most important denominator among the fusion proteins is the fusion peptide. In this review, work done in the last few years on the molecular mechanism of viral membrane fusion will be highlighted, focusing in particular on the role of the fusion peptide and the modification of the lipid bilayer structure. Much of what is known regarding the molecular mechanism of viral membrane fusion has been gained using liposomes as model systems in which the molecular components of the membrane and the environment are strictly controlled. Many amphilphilic peptides have a high affinity for lipid bilayers, but only a few sequences are able to induce membrane fusion. The presence of alpha-helical structure in at least part of the fusion peptide is strongly correlated with activity whereas, beta-structure tends to be less prevalent, associated with non-native experimental conditions, and more related to vesicle aggregation than fusion. The specific angle of insertion of the peptides into the membrane plane is also found to be an important characteristic for the fusion process. A shallow penetration, extending only to the central aliphatic core region, is likely responsible for the destabilization of the lipids required for coalescence of the apposing membranes and fusion.