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Structural basis of αE-catenin–F-actin catch bond behavior
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 exper...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588230/ https://www.ncbi.nlm.nih.gov/pubmed/32915141 http://dx.doi.org/10.7554/eLife.60878 |
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author | Xu, Xiao-Ping Pokutta, Sabine Torres, Megan Swift, Mark F Hanein, Dorit Volkmann, Niels Weis, William I |
author_facet | Xu, Xiao-Ping Pokutta, Sabine Torres, Megan Swift, Mark F Hanein, Dorit Volkmann, Niels Weis, William I |
author_sort | Xu, Xiao-Ping |
collection | PubMed |
description | 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 five-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. |
format | Online Article Text |
id | pubmed-7588230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-75882302020-10-28 Structural basis of αE-catenin–F-actin catch bond behavior Xu, Xiao-Ping Pokutta, Sabine Torres, Megan Swift, Mark F Hanein, Dorit Volkmann, Niels Weis, William I eLife Structural Biology and Molecular Biophysics 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 five-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. eLife Sciences Publications, Ltd 2020-09-11 /pmc/articles/PMC7588230/ /pubmed/32915141 http://dx.doi.org/10.7554/eLife.60878 Text en © 2020, Xu et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Structural Biology and Molecular Biophysics Xu, Xiao-Ping Pokutta, Sabine Torres, Megan Swift, Mark F Hanein, Dorit Volkmann, Niels Weis, William I Structural basis of αE-catenin–F-actin catch bond behavior |
title | Structural basis of αE-catenin–F-actin catch bond behavior |
title_full | Structural basis of αE-catenin–F-actin catch bond behavior |
title_fullStr | Structural basis of αE-catenin–F-actin catch bond behavior |
title_full_unstemmed | Structural basis of αE-catenin–F-actin catch bond behavior |
title_short | Structural basis of αE-catenin–F-actin catch bond behavior |
title_sort | structural basis of αe-catenin–f-actin catch bond behavior |
topic | Structural Biology and Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588230/ https://www.ncbi.nlm.nih.gov/pubmed/32915141 http://dx.doi.org/10.7554/eLife.60878 |
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