Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multimicrosecond, all-atom molecular dynamics simulations.

ABSTRACT: Platelet aggregation is the consequence of the binding of extracellular bivalent ligands such as fibrinogen and von Willebrand factor to the high affinity, active state of integrin αIIbβ3. This state is achieved through a so-called "inside-out" mechanism characterized by the membrane-assisted formation of a complex between the F2 and F3 subdomains of intracellular protein talin and the integrin β3 tail. Here, we present the results of multi-microsecond, all-atom molecular dynamics simulations carried on the complete transmembrane (TM) and C-terminal (CT) domains of αIIbβ3 integrin in an explicit lipid-water environment, and in the presence or absence of the talin-1 F2 and F3 subdomains. These large-scale simulations provide unprecedented molecular-level insights into the talin-driven insid

SUBMITTER: Provasi D 

PROVIDER: S-EPMC5156318 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature