Coarse-Grained Model of SNARE-Mediated Docking.

ABSTRACT: Synaptic transmission requires that vesicles filled with neurotransmitter molecules be docked to the plasma membrane by the SNARE protein complex. The SNARE complex applies attractive forces to overcome the long-range repulsion between the vesicle and membrane. To understand how the balance between the attractive and repulsive forces defines the equilibrium docked state we have developed a model that combines the mechanics of vesicle/membrane deformation with an apparently new coarse-grained model of the SNARE complex. The coarse-grained model of the SNARE complex is calibrated by comparison with all-atom molecular dynamics simulations as well as by force measurements in laser tweezer experiments. The model for vesicle/membrane interactions includes the forces produced by membrane deformation and hydration or electrostatic repulsion. Combining these two parts, the coarse-grained model of the SNARE complex with membrane mechanics, we study how the equilibrium docked state varies with the number of SNARE complexes. We find that a single SNARE complex is able to bring a typical synaptic vesicle to within a distance of ? 3 nm from the membrane. Further addition of SNARE complexes shortens this distance, but an overdocked state of >4-6 SNAREs actually increases the equilibrium distance.

SUBMITTER: Fortoul N 

PROVIDER: S-EPMC4423046 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature