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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...

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Autores principales: Xu, Xiao-Ping, Pokutta, Sabine, Torres, Megan, Swift, Mark F, Hanein, Dorit, Volkmann, Niels, Weis, William I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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