Structural highlights
2whv is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Related: | 2wbx, 2wd0, 2wcp |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[CAD23_MOUSE] Defects in Cdh23 are the cause of waltzer (v) phenotype. Waltzer mice are characterized by deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear.
Function
[CAD23_MOUSE] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining the proper organization of the stereocilia bundle of hair cells in the cochlea and the vestibule during late embryonic/early postnatal development. It is part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The hair-cell tip link, a fine filament directly conveying force to mechanosensitive transduction channels, is composed of two proteins, protocadherin-15 and cadherin-23, whose mutation causes deafness. However, their molecular structure, elasticity, and deafness-related structural defects are unknown. We present crystal structures of the first and second extracellular cadherin repeats of cadherin-23. Overall, structures show typical cadherin folds, but reveal an elongated N terminus that precludes classical cadherin interactions and contributes to an N-terminal Ca(2+)-binding site. The deafness mutation D101G, in the linker region between the repeats, causes a slight bend between repeats and decreases Ca(2+) affinity. Molecular dynamics simulations suggest that cadherin-23 repeats are stiff and that either removing Ca(2+) or mutating Ca(2+)-binding residues reduces rigidity and unfolding strength. The structures define an uncharacterized cadherin family and, with simulations, suggest mechanisms underlying inherited deafness and how cadherin-23 may bind with itself and with protocadherin-15 to form the tip link.
Structural determinants of cadherin-23 function in hearing and deafness.,Sotomayor M, Weihofen WA, Gaudet R, Corey DP Neuron. 2010 Apr 15;66(1):85-100. PMID:20399731[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Di Palma F, Holme RH, Bryda EC, Belyantseva IA, Pellegrino R, Kachar B, Steel KP, Noben-Trauth K. Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D. Nat Genet. 2001 Jan;27(1):103-7. PMID:11138008 doi:http://dx.doi.org/10.1038/83660
- ↑ Sotomayor M, Weihofen WA, Gaudet R, Corey DP. Structural determinants of cadherin-23 function in hearing and deafness. Neuron. 2010 Apr 15;66(1):85-100. PMID:20399731 doi:10.1016/j.neuron.2010.03.028
