Structural basis of αE-catenin-F-actin catch bond behavior
Abstract
Cell-cell and cell-matrix junctions transmit mechanical forces during tissue morphogenesis and homeostasis. α-Catenin links cell-cell adhesion complexes to the actin cytoskeleton, and mechanical load strengthens its binding to F-actin in a direction-sensitive manner. Specifically, optical trap experiments revealed that force promotes a transition between weak and strong actin-bound states. Here, we describe the cryo-electron microscopy structure of the F-actin-bound αE-catenin actin-binding domain, which in solution forms a 5-helix bundle. In the actin-bound structure, the first helix of the bundle dissociates and the remaining four helices and connecting loops rearrange to form the interface with actin. Deletion of the first helix produces strong actin binding in the absence of force, suggesting that the actin-bound structure corresponds to the strong state. Our analysis explains how mechanical force applied to αE-catenin or its homolog vinculin favors the strongly bound state, and the dependence of catch bond strength on the direction of applied force.
Data availability
The coordinates and cryo-EM map of the aE-catenin-F-actin complex have been deposited in the Protein Data Bank, identifiers 6WVT and EMD-21925, respectively
Article and author information
Author details
Funding
National Institutes of Health (GM118326)
- Dorit Hanein
- Niels Volkmann
- William I Weis
National Institutes of Health (GM131747)
- William I Weis
National Institutes of Health (S10-OD012372)
- Dorit Hanein
National Institutes of Health (S10-OD026926)
- Dorit Hanein
Pew Charitable Trusts (864K625)
- Dorit Hanein
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Xu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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