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Allosteric activation of vinculin by Talin

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 as...

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Main Authors: Franz, Florian (Author) , Tapia-Rojo, Rafael (Author) , Winograd-Katz, Sabina (Author) , Boujemaa-Paterski, Rajaa (Author) , Li, Wenhong (Author) , Unger, Tamar (Author) , Albeck, Shira (Author) , Aponte-Santamaria, Camilo (Author) , Garcia-Manyes, Sergi (Author) , Medalia, Ohad (Author) , Geiger, Benjamin (Author) , Gräter, Frauke (Author)
Format: Article (Journal)
Language:English
Published: 2023
In: Nature Communications
Year: 2023, Volume: 14, Pages: 1-16
ISSN:2041-1723
DOI:10.1038/s41467-023-39646-4
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-023-39646-4
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-023-39646-4
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Author Notes:Florian Franz, Rafael Tapia-Rojo, Sabina Winograd-Katz, Rajaa Boujemaa-Paterski, Wenhong Li, Tamar Unger, Shira Albeck, Camilo Aponte-Santamaria, Sergi Garcia-Manyes, Ohad Medalia, Benjamin Geiger & Frauke Gräter
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Summary: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.
Item Description:Veröffentlicht: 18. Juli 2023
Gesehen am 06.10.2023
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-023-39646-4

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