Allosteric activation of vinculin by talin

Florian Franz, Rafael Tapia Rojo*, Sabina Winograd-Katz, Rajaa Boujemaa-Paterski, wending li, tamar Unger, shira albeck, camilo aponte-santamaria, Sergi Garcia-Manyes, Ohad Medalia*, Benjamin geiger*, frauke grater*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
23 Downloads (Pure)

Abstract

The talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear. By combining single-molecule magnetic tweezers experiments, Molecular Dynamics simulations, actin-bundling assays, and adhesion assembly experiments in live cells, we here describe a two-ways allosteric network within vinculin as a regulator of the talin-vinculin interaction. We directly observe a maturation process of vinculin upon talin binding, which reinforces the binding to talin at a rate of 0.03 s−1. This allosteric transition can compete with force-induced dissociation of vinculin from talin only at forces up to 10 pN. Mimicking the allosteric activation by mutation yields a vinculin molecule that bundles actin and localizes to focal adhesions in a force-independent manner. Hence, the allosteric switch confines talin-vinculin interactions and focal adhesion build-up to intermediate force levels. The ‘allosteric vinculin mutant’ is a valuable molecular tool to further dissect the mechanical and biochemical signalling circuits at focal adhesions and elsewhere.
Original languageEnglish
Article number4311
JournalNature Communications
Volume14
Issue number4311
DOIs
Publication statusPublished - 18 Jul 2023

Keywords

  • Vinculin
  • Talin
  • Mechanotransduction

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