Force-dependent conformational switch of α -catenin controls vinculin binding

Yao M, Qiu W, Liu R, Efremov AK, Cong P, Seddiki R, Payre M, Lim CT, Ladoux B, Mège RM, Yan J (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 5

Article Number: 4525

DOI: 10.1038/ncomms5525

Abstract

Force sensing at cadherin-mediated adhesions is critical for their proper function. α-Catenin, which links cadherins to actomyosin, has a crucial role in this mechanosensing process. It has been hypothesized that force promotes vinculin binding, although this has never been demonstrated. X-ray structure further suggests that α-Catenin adopts a stable auto-inhibitory conformation that makes the vinculin-binding site inaccessible. Here, by stretching single acatenin molecules using magnetic tweezers, we show that the subdomains MI vinculinbinding domain (VBD) to MIII unfold in three characteristic steps: a reversible step at B5pN and two non-equilibrium steps at 10-15 pN. 5 pN unfolding forces trigger vinculin binding to the MI domain in a 1:1 ratio with nanomolar affinity, preventing MI domain refolding after force is released. Our findings demonstrate that physiologically relevant forces reversibly unfurl acatenin, activating vinculin binding, which then stabilizes α-Catenin in its open conformation, transforming force into a sustainable biochemical signal.© 2014 Macmillan Publishers Limited. All rights reserved.

Authors with CRIS profile

Benoit Ladoux

Involved external institutions

National University of Singapore (NUS) SG Singapore (SG) Institut Jacques Monod (IJM) FR France (FR)

How to cite

APA:

Yao, M., Qiu, W., Liu, R., Efremov, A.K., Cong, P., Seddiki, R.,... Yan, J. (2014). Force-dependent conformational switch of α -catenin controls vinculin binding. Nature Communications, 5. https://doi.org/10.1038/ncomms5525

MLA:

Yao, Mingxi, et al. "Force-dependent conformational switch of α -catenin controls vinculin binding." Nature Communications 5 (2014).

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