1. Structural Biology and Molecular Biophysics
Download icon

Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5

  1. Jingpeng Ge
  2. Johannes Elferich
  3. April Goehring
  4. Joy Zhao
  5. Peter Schuck
  6. Eric Gouaux  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. National Institutes of Health, United States
Research Article
  • Cited 4
  • Views 2,089
  • Annotations
Cite this article as: eLife 2018;7:e38770 doi: 10.7554/eLife.38770

Abstract

Hearing and balance involve the transduction of mechanical stimuli into electrical signals by deflection of bundles of stereocilia linked together by protocadherin 15 (PCDH15) and cadherin 23 'tip links'. PCDH15 transduces tip link tension into opening of a mechano-electrical transduction (MET) ion channel. PCDH15 also interacts with LHFPL5, a candidate subunit of the MET channel. Here we illuminate the PCDH15-LHFPL5 structure, showing how the complex is composed of PCDH15 and LHFPL5 subunit pairs related by a 2-fold axis. The extracellular cadherin domains define a mobile tether coupled to a rigid, 2-fold symmetric 'collar' proximal to the membrane bilayer. LHFPL5 forms extensive interactions with the PCDH15 transmembrane helices and stabilizes the overall PCDH15-LHFPL5 assembly. Our studies illuminate the architecture of the PCDH15-LHFPL5 complex, localize mutations associated with deafness, and shed new light on how forces in the PCDH15 tether may be transduced into the stereocilia membrane.

Article and author information

Author details

  1. Jingpeng Ge

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6164-1221
  2. Johannes Elferich

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9911-706X
  3. April Goehring

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Joy Zhao

    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Peter Schuck

    Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8859-6966
  6. Eric Gouaux

    Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    gouauxe@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8549-2360

Funding

National Institutes of Health (NIBIB intramural research program)

  • Joy Zhao
  • Peter Schuck

Howard Hughes Medical Institute

  • Eric Gouaux

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. William I Weis, Stanford University Medical Center, United States

Publication history

  1. Received: May 30, 2018
  2. Accepted: July 31, 2018
  3. Accepted Manuscript published: August 2, 2018 (version 1)
  4. Version of Record published: August 14, 2018 (version 2)
  5. Version of Record updated: September 12, 2018 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,089
    Page views
  • 545
    Downloads
  • 4
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics
    Nancy L Meyer et al.
    Research Article Updated
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Nicolas Bigot et al.
    Research Article Updated