1. Structural Biology and Molecular Biophysics
  2. Cell Biology
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Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin

  1. Haiyang Liu
  2. Jianchao Li
  3. Manmeet H Raval
  4. Ningning Yao
  5. Xiaoying Deng
  6. Qing Lu
  7. Si Nie
  8. Wei Feng
  9. Jun Wan
  10. Christopher M Yengo
  11. Wei Liu
  12. Mingjie Zhang  Is a corresponding author
  1. Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, China
  2. Hong Kong University of Science and Technology, China
  3. Pennsylvania State University College of Medicine, United States
  4. Chinese Academy of Sciences, China
Research Article
  • Cited 14
  • Views 1,832
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Cite this article as: eLife 2016;5:e12856 doi: 10.7554/eLife.12856

Abstract

Class III myosins (Myo3) and actin-bundling protein Espin play critical roles in regulating the development and maintenance of stereocilia in vertebrate hair cells, and their defects cause hereditary hearing impairments. Myo3 interacts with Espin1 through its tail homology I motif (THDI), however it is not clear how Myo3 specifically acts through Espin1 to regulate the actin bundle assembly and stabilization. Here we discover that Myo3 THDI contains a pair of repeat sequences capable of independently and strongly binding to the ankyrin repeats of Espin1, revealing an unexpected Myo3-mediated cross-linking mechanism of Espin1. The structures of Myo3 in complex with Espin1 not only elucidate the mechanism of the binding, but also reveal a Myo3-induced release of Espin1 auto-inhibition mechanism. We also provide evidence that Myo3-mediated cross-linking can further promote actin fiber bundling activity of Espin1.

Article and author information

Author details

  1. Haiyang Liu

    Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
    Competing interests
    No competing interests declared.
  2. Jianchao Li

    Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China
    Competing interests
    No competing interests declared.
  3. Manmeet H Raval

    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, United States
    Competing interests
    No competing interests declared.
  4. Ningning Yao

    Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
    Competing interests
    No competing interests declared.
  5. Xiaoying Deng

    Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
    Competing interests
    No competing interests declared.
  6. Qing Lu

    Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China
    Competing interests
    No competing interests declared.
  7. Si Nie

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    No competing interests declared.
  8. Wei Feng

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    No competing interests declared.
  9. Jun Wan

    Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
    Competing interests
    No competing interests declared.
  10. Christopher M Yengo

    Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, United States
    Competing interests
    No competing interests declared.
  11. Wei Liu

    Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
    Competing interests
    No competing interests declared.
  12. Mingjie Zhang

    Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
    For correspondence
    mzhang@ust.hk
    Competing interests
    Mingjie Zhang, Reviewing editor, eLife.

Reviewing Editor

  1. Cynthia Wolberger, Johns Hopkins University, United States

Publication history

  1. Received: November 5, 2015
  2. Accepted: January 18, 2016
  3. Accepted Manuscript published: January 19, 2016 (version 1)
  4. Version of Record published: February 5, 2016 (version 2)
  5. Version of Record updated: July 6, 2016 (version 3)

Copyright

© 2016, Liu 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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