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Structure paper

TitleStructure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5.
Journal, issue, pagesElife, Vol. 7, Year 2018
Publish dateAug 2, 2018
AuthorsJingpeng Ge / Johannes Elferich / April Goehring / Huaying Zhao / Peter Schuck / Eric Gouaux /
PubMed AbstractHearing 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 ...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.
External linksElife / PubMed:30070639 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.399 - 11.33 Å
Structure data

7327

6c13

EMDB-7327, PDB-6c13:
CryoEM structure of mouse PCDH15-4EC-LHFPL5 complex
Method: EM (single particle) / Resolution: 11.33 Å

7328

6c14

EMDB-7328, PDB-6c14:
CryoEM structure of mouse PCDH15-1EC-LHFPL5 complex
Method: EM (single particle) / Resolution: 4.5 Å

PDB-6c10:
Crystal structure of mouse PCDH15 EC11-EL
Method: X-RAY DIFFRACTION / Resolution: 1.399 Å

Chemicals

ChemComp-MAN:
alpha-D-mannopyranose / Mannose

ChemComp-HOH:
WATER / Water

Source
  • mus musculus (house mouse)
Keywordsmembrane protein / metal transport / PCDH15 / LHFPL5 / protocadherin / tip link / hair cell / TMHS / hearing

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