We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

6c13

From Proteopedia

Revision as of 07:51, 17 October 2024 by OCA (Talk | contribs)

(diff) ←Older revision | Current revision (diff) | Newer revision→ (diff)

Jump to: navigation, search

CryoEM structure of mouse PCDH15-4EC-LHFPL5 complex

6c13, resolution 11.33Å

Structural highlights

6c13 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 11.33Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PCD15_MOUSE Defects in Pcdh15 are the cause of the Ames waltzer (av) phenotype. It is characterized by deafness and a balance disorder, associated with the degeneration of inner ear neuroepithelia.

Function

PCD15_MOUSE Calcium-dependent cell-adhesion protein. Required for inner ear neuroepithelial cell elaboration and cochlear function. Probably involved in the maintenance of normal retinal function.

Publication Abstract from PubMed

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.

Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5.,Ge J, Elferich J, Goehring A, Zhao H, Schuck P, Gouaux E Elife. 2018 Aug 2;7. pii: 38770. doi: 10.7554/eLife.38770. PMID:30070639^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ge J, Elferich J, Goehring A, Zhao H, Schuck P, Gouaux E. Structure of mouse protocadherin 15 of the stereocilia tip link in complex with LHFPL5. Elife. 2018 Aug 2;7. pii: 38770. doi: 10.7554/eLife.38770. PMID:30070639 doi:http://dx.doi.org/10.7554/eLife.38770