Structural basis of αE-catenin-F-actin catch bond behavior
- Scintillon Institute, United States
- Stanford University, United States
- Stanford University School of Medicine, United States
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.
Reviewing Editor
- Christopher P Hill, University of Utah School of Medicine, United States
Version history
- Received: July 9, 2020
- Accepted: September 9, 2020
- Accepted Manuscript published: September 11, 2020 (version 1)
- Version of Record published: October 26, 2020 (version 2)
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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Structural basis of αE-catenin-F-actin catch bond behavior
eLife 9:e60878.
https://doi.org/10.7554/eLife.60878
Further reading
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- Cell Biology
- Structural Biology and Molecular Biophysics
The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulated. Here we employ both optical trapping and biochemical reconstitution with myosin motor proteins to show single piconewton forces applied solely to F-actin enhance binding by the human version of the essential cell-cell adhesion protein αE-catenin but not its homolog vinculin. Cryo-electron microscopy structures of both proteins bound to F-actin reveal unique rearrangements that facilitate their flexible C-termini refolding to engage distinct interfaces. Truncating α-catenin’s C-terminus eliminates force-activated F-actin binding, and addition of this motif to vinculin confers force-activated binding, demonstrating that α-catenin’s C-terminus is a modular detector of F-actin tension. Our studies establish that piconewton force on F-actin can enhance partner binding, which we propose mechanically regulates cellular adhesion through α-catenin.
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- Cell Biology
- Structural Biology and Molecular Biophysics
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