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Direct simulation of protein-mediated vesicle fusion: lung surfactant protein B.

ABSTRACT: We simulated spontaneous fusion of small unilamellar vesicles mediated by lung surfactant protein B (SP-B) using the MARTINI force field. An SP-B monomer triggers fusion events by anchoring two vesicles and facilitating the formation of a lipid bridge between the proximal leaflets. Once a lipid bridge is formed, fusion proceeds via a previously described stalk - hemifusion diaphragm - pore-opening pathway. In the absence of protein, fusion of vesicles was not observed in either unbiased simulations or upon application of a restraining potential to maintain the vesicles in close proximity. The shape of SP-B appears to enable it to bind to two vesicles at once, forcing their proximity, and to facilitate the initial transfer of lipids to form a high-energy hemifusion intermediate. Our results may provide insight into more general mechanisms of protein-mediated membrane fusion, and a possible role of SP-B in the secretory pathway and transfer of lung surfactant to the gas exchange interface.

SUBMITTER: Baoukina S

PROVIDER: S-EPMC3042587 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Direct simulation of protein-mediated vesicle fusion: lung surfactant protein B.

Baoukina Svetlana S Tieleman D Peter DP

Biophysical journal 20101001 7

We simulated spontaneous fusion of small unilamellar vesicles mediated by lung surfactant protein B (SP-B) using the MARTINI force field. An SP-B monomer triggers fusion events by anchoring two vesicles and facilitating the formation of a lipid bridge between the proximal leaflets. Once a lipid bridge is formed, fusion proceeds via a previously described stalk - hemifusion diaphragm - pore-opening pathway. In the absence of protein, fusion of vesicles was not observed in either unbiased simulati ...[more]

PMID: 20923647

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