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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354202/ https://www.ncbi.nlm.nih.gov/pubmed/37463895 http://dx.doi.org/10.1038/s41467-023-39646-4 |
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author | Franz, Florian Tapia-Rojo, Rafael Winograd-Katz, Sabina Boujemaa-Paterski, Rajaa Li, Wenhong Unger, Tamar Albeck, Shira Aponte-Santamaria, Camilo Garcia-Manyes, Sergi Medalia, Ohad Geiger, Benjamin Gräter, Frauke |
author_facet | Franz, Florian Tapia-Rojo, Rafael Winograd-Katz, Sabina Boujemaa-Paterski, Rajaa Li, Wenhong Unger, Tamar Albeck, Shira Aponte-Santamaria, Camilo Garcia-Manyes, Sergi Medalia, Ohad Geiger, Benjamin Gräter, Frauke |
author_sort | Franz, Florian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10354202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103542022023-07-20 Allosteric activation of vinculin by talin Franz, Florian Tapia-Rojo, Rafael Winograd-Katz, Sabina Boujemaa-Paterski, Rajaa Li, Wenhong Unger, Tamar Albeck, Shira Aponte-Santamaria, Camilo Garcia-Manyes, Sergi Medalia, Ohad Geiger, Benjamin Gräter, Frauke Nat Commun Article 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. Nature Publishing Group UK 2023-07-18 /pmc/articles/PMC10354202/ /pubmed/37463895 http://dx.doi.org/10.1038/s41467-023-39646-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Franz, Florian Tapia-Rojo, Rafael Winograd-Katz, Sabina Boujemaa-Paterski, Rajaa Li, Wenhong Unger, Tamar Albeck, Shira Aponte-Santamaria, Camilo Garcia-Manyes, Sergi Medalia, Ohad Geiger, Benjamin Gräter, Frauke Allosteric activation of vinculin by talin |
title | Allosteric activation of vinculin by talin |
title_full | Allosteric activation of vinculin by talin |
title_fullStr | Allosteric activation of vinculin by talin |
title_full_unstemmed | Allosteric activation of vinculin by talin |
title_short | Allosteric activation of vinculin by talin |
title_sort | allosteric activation of vinculin by talin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354202/ https://www.ncbi.nlm.nih.gov/pubmed/37463895 http://dx.doi.org/10.1038/s41467-023-39646-4 |
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