Molecular dynamics simulations reveal how vinculin refolds partially unfolded talin rod helices to stabilize them against mechanical force

• DOI: 10.1371/journal.pcbi.1012341
• Publication Date: 2024-08-07T17:43:53Z
• Authors: Vasyl V. Mykuliak; Rolle Rahikainen; Neil J. Ball; Giovanni Bussi; Benjamin T. Goult; Vesa P. Hytönen
• Keywords: Vinculin; Molecular mechanics

Vinculin binds to specific sites of mechanically unfolded talin rod domains reinforce the coupling cell’s exterior its force generation machinery. Force-dependent vinculin–talin complexation and dissociation was previously observed as contraction or extension respectively using magnetic tweezers. However, structural mechanism underlying vinculin recognition binding (VBSs) in remains unknown. Using molecular dynamics simulations, we demonstrate that a VBS dynamically refolds under force, can recognize bind partially states. enables refolding strained stabilizes folded α-helical conformation, providing resistance against mechanical stress. Together, these results provide an understanding proteins by insight into initial moments how during assembly this mechanosensing meshwork.