Buchumschlag

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Franz, Florian (VerfasserIn) , Tapia-Rojo, Rafael (VerfasserIn) , Winograd-Katz, Sabina (VerfasserIn) , Boujemaa-Paterski, Rajaa (VerfasserIn) , Li, Wenhong (VerfasserIn) , Unger, Tamar (VerfasserIn) , Albeck, Shira (VerfasserIn) , Aponte-Santamaria, Camilo (VerfasserIn) , Garcia-Manyes, Sergi (VerfasserIn) , Medalia, Ohad (VerfasserIn) , Geiger, Benjamin (VerfasserIn) , Gräter, Frauke (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2023
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
Volltext
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
Beschreibung
Zusammenfassung: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.
Beschreibung:Veröffentlicht: 18. Juli 2023
Gesehen am 06.10.2023
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-023-39646-4

Ähnliche Einträge