How force might activate talin's vinculin binding sites: SMD reveals a structural mechanism.

ABSTRACT: Upon cell adhesion, talin physically couples the cytoskeleton via integrins to the extracellular matrix, and subsequent vinculin recruitment is enhanced by locally applied tensile force. Since the vinculin binding (VB) sites are buried in the talin rod under equilibrium conditions, the structural mechanism of how vinculin binding to talin is force-activated remains unknown. Taken together with experimental data, a biphasic vinculin binding model, as derived from steered molecular dynamics, provides high resolution structural insights how tensile mechanical force applied to the talin rod fragment (residues 486-889 constituting helices H1-H12) might activate the VB sites. Fragmentation of the rod into three helix subbundles is prerequisite to the sequential exposure of VB helices to water. F

SUBMITTER: Hytonen VP 

PROVIDER: S-EPMC2242828 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature