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

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.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [2]; ORCiD logo [3]
  1. Vollum Institute, Oregon Health & Science University, Portland, United States
  2. Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States
  3. Vollum Institute, Oregon Health & Science University, Portland, United States; Howard Hughes Medical Institute, Oregon Health & Science University, Portland, United States
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHHHMI
OSTI Identifier:
1467724
Resource Type:
Journal Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 7; Journal Issue: 08, 2018; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Ge, Jingpeng, Elferich, Johannes, Goehring, April, Zhao, Huaying, Schuck, Peter, and Gouaux, Eric. Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5. United States: N. p., 2018. Web. doi:10.7554/eLife.38770.
Ge, Jingpeng, Elferich, Johannes, Goehring, April, Zhao, Huaying, Schuck, Peter, & Gouaux, Eric. Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5. United States. doi:10.7554/eLife.38770.
Ge, Jingpeng, Elferich, Johannes, Goehring, April, Zhao, Huaying, Schuck, Peter, and Gouaux, Eric. Thu . "Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5". United States. doi:10.7554/eLife.38770.
@article{osti_1467724,
title = {Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5},
author = {Ge, Jingpeng and Elferich, Johannes and Goehring, April and Zhao, Huaying and Schuck, Peter and Gouaux, Eric},
abstractNote = {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.},
doi = {10.7554/eLife.38770},
journal = {eLife},
issn = {2050-084X},
number = 08, 2018,
volume = 7,
place = {United States},
year = {2018},
month = {8}
}

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