SECRETORY AND VIRAL FUSION MAY SHARE MECHANISTIC EVENTS WITH FUSION BETWEEN CURVED LIPID BILAYERS

Activation energies for the individual steps of secretory and viral fu sion are reported to he large [Oberhauser, A. F,, Monck, J, R. & Ferna ndez, J, M, (1992) Biophys. J. 61, 800-809; Clague, M, J,, Schoch, C,, Zech, L, & Blumenthal, R. (1990) Biochemistry 29, 1303-1308]. Underst anding the cause for these large activation energies is crucial to def ining the mechanisms of these two types of biological membrane fusion, We showed recently that the fusion of protein-free model lipid bilaye rs mimics the sequence of steps observed during secretory and viral fu sion, suggesting that these processes mag involve common lipid, rather than protein, rearrangements. To test for this possibility, we determ ined the activation energies for the three steps that we were able to distinguish as contributing to the fusion of protein-free model lipid bilayers, Activation energies for lipid rearrangements associated with formation of the reversible first intermediate, with conversion of th is to a semi-stable second intermediate, and with irreversible fusion pore formation were 37 kcal/mol, 27 kcal/moI, and 22 kcal/mol, respect ively. The first and last of these were comparable to the activation e nergies observed for membrane lipid exchange (42 kcal/moI) during vira l fusion and for the rate of fusion pore opening during secretory gran ule release (23 kcal/mol), This striking similarity suggests strongly that the basic molecular processes involved in secretory and viral fus ion involve a set of lipid molecule rearrangements that also are invol ved in model membrane fusion.