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TITLE:
Fusion: Protein Machines and Lipid Materials
SPEAKER:
Professor Barry R. Lentz,
TIME: Thursday Mar. 31, 2005 at 4 PM
PLACE: George P. Williams, Jr. Lecture Hall, (Olin 101)
University of North Carolina at Chapel Hill
Poly (ethylene glycol) (PEG)-mediated fusion of model membrane vesicles serves as a model of biomembrane fusion. This process proceeds via at least two intermediates that involve arrangements of lipid molecules unlike those present in the lamellar phase characteristic of biomembrane structure. The probability of forming a fusion pore is thus defined by the probabilities of four events: 1] formation of inter-bilayer contact, 2] conversion of a contact into an unstable/reversible fusion intermediate ("stalk"), 3] maturation of the initial intermediate to a stable intermediate, 4] conversion of either intermediate to a pore. In terms of this "stalk model", the major free energy barriers to conversion of the initial to final intermediate are the free energy of bending a lamellar phase and the free energy of distorting a smoothly bent bilayer to a non-lamellar structure. The later term is described in terms of an "interstice" free energy. Kinetic evidence supports application of this model to vesicle fusion. If this model applies to biomembrane fusion, then protein fusion machines should increase the probability of one or more of these events. The portions of viral fusion proteins that contact membranes enhance the rate of pore formation and thus lower the free energy barrier between the first intermediate and a fusion pore, probably due to lowering the interstice free energy. Space-filling, flexible hydrocarbons are known to also lower this free energy. Reconstituted exocytotic SNARE complexes also enhance the rate of fusion a factor of two, suggesting that this protein complex also lowers the free energy barrier(s) between the initial intermediate and a pore. The effects of fusion proteins are thus similar to the effects of small hydrocarbons that promote pore formation by filling space in the membrane. Supported by GM32707.