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| | ==Crystal Structure of Mouse Cadherin-23 EC24-25== | | ==Crystal Structure of Mouse Cadherin-23 EC24-25== |
| - | <StructureSection load='5vt8' size='340' side='right' caption='[[5vt8]], [[Resolution|resolution]] 2.92Å' scene=''> | + | <StructureSection load='5vt8' size='340' side='right'caption='[[5vt8]], [[Resolution|resolution]] 2.92Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vt8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VT8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VT8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vt8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VT8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cdh23 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cdh23 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vt8 OCA], [http://pdbe.org/5vt8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vt8 RCSB], [http://www.ebi.ac.uk/pdbsum/5vt8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vt8 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5vt8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vt8 OCA], [https://pdbe.org/5vt8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vt8 RCSB], [https://www.ebi.ac.uk/pdbsum/5vt8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vt8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CAD23_MOUSE 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. | + | [[https://www.uniprot.org/uniprot/CAD23_MOUSE 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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CAD23_MOUSE 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.<ref>PMID:11138008</ref> | + | [[https://www.uniprot.org/uniprot/CAD23_MOUSE 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.<ref>PMID:11138008</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5vt8" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5vt8" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cadherin 3D structures|Cadherin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Jaiganesh, A]] | | [[Category: Jaiganesh, A]] |
| Structural highlights
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]
Publication Abstract from PubMed
Cadherin-23 (CDH23) is an essential component of hair-cell tip links, fine filaments that mediate inner-ear mechanotransduction. The extracellular domain of CDH23 forms about three-fourths of the tip link with 27 extracellular cadherin (EC) repeats that are structurally similar but not identical to each other. Calcium (Ca(2+)) coordination at the EC linker regions is key for tip-link elasticity and function. There are approximately 116 sites in CDH23 affected by deafness-causing mutations, many of which alter conserved Ca(2+)-binding residues. Here we present crystal structures showing 18 CDH23 EC repeats, including the most and least conserved, a fragment carrying disease mutations, and EC repeats with non-canonical Ca(2+)-binding motif sequences and unusual secondary structure. Complementary experiments show deafness mutations' effects on stability and affinity for Ca(2+). Additionally, a model of nine contiguous CDH23 EC repeats reveals helicity and potential parallel dimerization faces. Overall, our studies provide detailed structural insight into CDH23 function in mechanotransduction.
Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness.,Jaiganesh A, De-la-Torre P, Patel AA, Termine DJ, Velez-Cortes F, Chen C, Sotomayor M Structure. 2018 Jun 27. pii: S0969-2126(18)30209-0. doi:, 10.1016/j.str.2018.06.003. PMID:30033219[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Jaiganesh A, De-la-Torre P, Patel AA, Termine DJ, Velez-Cortes F, Chen C, Sotomayor M. Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness. Structure. 2018 Jun 27. pii: S0969-2126(18)30209-0. doi:, 10.1016/j.str.2018.06.003. PMID:30033219 doi:http://dx.doi.org/10.1016/j.str.2018.06.003
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