1. Structural Biology and Molecular Biophysics
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Structural basis of αE-catenin-F-actin catch bond behavior

  1. Xiao-Ping Xu
  2. Sabine Pokutta
  3. Megan Torres
  4. Mark F Swift
  5. Dorit Hanein  Is a corresponding author
  6. Niels Volkmann  Is a corresponding author
  7. William I Weis  Is a corresponding author
  1. Scintillon Institute, United States
  2. Stanford University, United States
  3. Stanford University School of Medicine, United States
Research Article
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Cite this article as: eLife 2020;9:e60878 doi: 10.7554/eLife.60878

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

  1. Xiao-Ping Xu

    Scintillon Institute, Scintillon Institute, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sabine Pokutta

    Department of Structural Biology, Stanford University, Stanford, CA, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Megan Torres

    Structural Biology and Molecular & Cellular Physiology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mark F Swift

    Scintillon Institute, Scintillon Institute, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dorit Hanein

    Scintillon Institute, Scintillon Institute, San Diego, United States
    For correspondence
    dorit@scintillon.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6072-4946
  6. Niels Volkmann

    Scintillon Institute, Scintillon Institute, San Diego, United States
    For correspondence
    niels@sbpdiscovery.org
    Competing interests
    The authors declare that no competing interests exist.
  7. William I Weis

    Departments of Structural Biology and of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States
    For correspondence
    weis@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5583-6150

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

  1. Christopher P Hill, University of Utah School of Medicine, United States

Publication history

  1. Received: July 9, 2020
  2. Accepted: September 9, 2020
  3. Accepted Manuscript published: September 11, 2020 (version 1)
  4. 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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