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Allosteric activation of vinculin by talin

Author

Listed:
  • Florian Franz

    (Heidelberg Institute for Theoretical Studies (HITS)
    Heidelberg University, Mathematikon, INF 205)

  • Rafael Tapia-Rojo

    (King’s College London
    The Francis Crick Institute)

  • Sabina Winograd-Katz

    (Weizmann Institute of Science)

  • Rajaa Boujemaa-Paterski

    (University of Zurich)

  • Wenhong Li

    (Weizmann Institute of Science)

  • Tamar Unger

    (Weizmann Institute of Science)

  • Shira Albeck

    (Weizmann Institute of Science)

  • Camilo Aponte-Santamaria

    (Heidelberg Institute for Theoretical Studies (HITS)
    Heidelberg University, Mathematikon, INF 205)

  • Sergi Garcia-Manyes

    (King’s College London
    The Francis Crick Institute)

  • Ohad Medalia

    (University of Zurich)

  • Benjamin Geiger

    (Weizmann Institute of Science)

  • Frauke Gräter

    (Heidelberg Institute for Theoretical Studies (HITS)
    Heidelberg University, Mathematikon, INF 205
    Heidelberg University, INF 225)

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.

Suggested Citation

  • 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 , 2023. "Allosteric activation of vinculin by talin," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39646-4
    DOI: 10.1038/s41467-023-39646-4
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    References listed on IDEAS

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    1. Mingxi Yao & Benjamin T. Goult & Benjamin Klapholz & Xian Hu & Christopher P. Toseland & Yingjian Guo & Peiwen Cong & Michael P. Sheetz & Jie Yan, 2016. "The mechanical response of talin," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    2. Shubhasis Haldar & Rafael Tapia-Rojo & Edward C. Eckels & Jessica Valle-Orero & Julio M. Fernandez, 2017. "Trigger factor chaperone acts as a mechanical foldase," Nature Communications, Nature, vol. 8(1), pages 1-7, December.
    3. Tina Izard & Gwyndaf Evans & Robert A. Borgon & Christina L. Rush & Gerard Bricogne & Philippe R. J. Bois, 2004. "Vinculin activation by talin through helical bundle conversion," Nature, Nature, vol. 427(6970), pages 171-175, January.
    4. Carsten Grashoff & Brenton D. Hoffman & Michael D. Brenner & Ruobo Zhou & Maddy Parsons & Michael T. Yang & Mark A. McLean & Stephen G. Sligar & Christopher S. Chen & Taekjip Ha & Martin A. Schwartz, 2010. "Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics," Nature, Nature, vol. 466(7303), pages 263-266, July.
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