Conformational states during vinculin unlocking differentially regulate focal adhesion properties

Dror S. Chorev, Tova Volberg, Ariel Livne, Miriam Eisenstein, Bruno Martins, Zvi Kam, Brigitte M. Jockusch, Ohad Medalia, Michal Sharon, Benny Geiger

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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 detailed molecular mechanisms underlying FA mechanosensitivity are still unclear. Besides talin, another key candidate for regulating FA-associated mechanosensing, is vinculin, a prominent FA component, which possesses either closed (“auto-inhibited”) or open (“active”) conformation. A direct experimental demonstration, however, of the conformational transition between the two states is still absent. In this study, we combined multiple structural and biological approaches to probe the transition from the auto-inhibited to the active conformation, and determine its effects on FA structure and dynamics. We further show that the transition from a closed to an open conformation requires two sequential steps that can differentially regulate FA growth and stability.

Original languageEnglish
Article number2693
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2018

ASJC Scopus subject areas

  • General

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