Architecture of native protocadherin-15 in complex with LHFPL5
EMSL Project ID
51212
Abstract
Mechanotransduction machinery located at the tips of hair bundles in the inner ear are responsible for oursensations of movement and sound. Each bundle is composed of stereocilia that are connected by tip-links, extracellular protein filaments made up of protocadherin-15 (PCDH15) bound to cadherin-23 (CDH23). Deflection of the hair bundle by sound and fluid movement leads to opening of the mechanotransduction (MET) complex located at the lower tip-link insertion site, resulting in an electrical signal. Currently, there is no structural information available for the native MET complex, which limits our understanding of how it functions. The objective of this project is to elucidate the structure of native PCDH15 bound to LHFPL5, another MET complex subunit, from mouse cochlea. We have developed methods that allow us to isolate the PCDH15/LHFPL5 complex from tissue for structural determination by single particle cryo-EM. Our work will provide insight into the architecture of two essential MET subunits and their contribution to the overall mechanism of mechanotransduction.
Project Details
Start Date
2019-12-20
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members