Differential Membrane Binding Mechanics of Synaptotagmin Isoforms Observed in Atomic Detail.

ABSTRACT: Synaptotagmin (Syt) is a membrane-associated protein involved in vesicle fusion through the SNARE complex that is found throughout the human body in 17 different isoforms. These isoforms have two membrane-binding C2 domains, which sense Ca²⁺ and thereby promote anionic membrane binding and lead to vesicle fusion. Through molecular dynamics simulations using the highly mobile membrane mimetic acclerated bilayer model, we have investigated how small protein sequence changes in the Ca²⁺-binding loops of the C2 domains may give rise to the experimentally determined difference in binding kinetics between Syt-1 and Syt-7 isoforms. Syt-7 C2 domains are found to form more close contacts with anionic phospholipid headgroups, particularly in loop 1, where an additional positive

SUBMITTER: Vermaas JV 

PROVIDER: S-EPMC5557660 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature