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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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2023
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| In: |
Nature Communications
Year: 2023, Jahrgang: 14, Pages: 1-16 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-023-39646-4 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a Allosteric activation of vinculin by Talin |c 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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| 520 | |a 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. | ||
| 650 | 4 | |a Computational biophysics | |
| 650 | 4 | |a Focal adhesion | |
| 650 | 4 | |a Single-molecule biophysics | |
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| 700 | 1 | |a Winograd-Katz, Sabina |e VerfasserIn |4 aut | |
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