PT  - JOURNAL ARTICLE
AU  - Dror S. Chorev
AU  - Tova Volberg
AU  - Ariel Livne
AU  - Miriam Eisenstein
AU  - Bruno Martins
AU  - Zvi Kam
AU  - Brigitte M. Jockusch
AU  - Ohad Medalia
AU  - Michal Sharon
AU  - Benny Geiger
TI  - Conformational states during vinculin unlocking differentially regulate focal adhesion properties
AID  - 10.1101/176586
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 176586
4099  - http://biorxiv.org/content/early/2017/08/16/176586.short
4100  - http://biorxiv.org/content/early/2017/08/16/176586.full
AB  - Focal adhesions (FAs) are multi-protein complexes that connect the actin cytoskeleton to the extracellular matrix, via integrin receptors. The growth, stability and adhesive functionality of these structures are tightly regulated by mechanical stress, yet, despite the extensive characterization of the integrin adhesome, the mechanisms underlying FA mechanosensitivity are still poorly understood. One of the key candidates for regulating FA-associated mechanosensing is vinculin, a prominent FA component, which was proposed to possess either closed (“auto-inhibited”) or open (active) conformations. However, a direct demonstration of the nature of conformational transition between the two states is still absent. In this study we combined multiple structural and biological approaches to probe the transition from auto-inhibited to active conformation, and determine its effects on FA structure and dynamics. We further show here that the closed to open transition requires two sequential steps that can differentially regulate FA growth and stability.