A remarkable mechanism for #DisturbedFlow disruption of #EndothelialCell Junction in #Atherosclerosis

Disturbed Flow-activated GRK2 phosphorylates #Vinculin Ser721-> a closed conformation of Vinculin
->⏬VE-cad junction

Dr. Jeng-Jiann Chiu lab Euro Heart J 2022
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac647/6830649

"Single-molecule magnetic tweezers to capture over a million individual transitions as a single talin protein unfolds and refolds under force in equilibrium. When observed at classically probed timescales, talin folds in an apparently uncomplicated two-state manner. As the sampling time extends from minutes to days, the underlying energy landscape exhibits gradually larger signatures of complexity, involving a finite number of well-defined rare conformations.[...]The physiological relevance of each distinct conformation can be connected to the binding of the cytoskeletal protein vinculin, suggesting an extra layer of complexity in talin-mediated mechanotransduction."
https://www.nature.com/articles/s41567-022-01808-4
#StructuralBiology #Talin #Vinculin #MechanoTransduction #MechanoBiology #Cytoskeleton