| Autor: |
Chorev DS; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel., Volberg T; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel., Livne A; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel., Eisenstein M; Chemical Research Support, Weizmann Institute of Science, Rehovot, 7610001, Israel., Martins B; Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland., Kam Z; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel., Jockusch BM; Department of Cell Biology, Zoological Institute, Technical University of Braunschweig, D-38092, Braunschweig, Germany., Medalia O; Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.; Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, 84105, Israel., Sharon M; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel. michal.sharon@weizmann.ac.il., Geiger B; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel. benny.geiger@weizmann.ac.il. |
| Abstrakt: |
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. |
