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| | <StructureSection load='4aq8' size='340' side='right'caption='[[4aq8]], [[Resolution|resolution]] 2.63Å' scene=''> | | <StructureSection load='4aq8' size='340' side='right'caption='[[4aq8]], [[Resolution|resolution]] 2.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4aq8]] 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=4AQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AQ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4aq8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AQ8 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.63Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wbx|2wbx]], [[2wcp|2wcp]], [[2wd0|2wd0]], [[2whv|2whv]], [[4apx|4apx]], [[4aqa|4aqa]], [[4aqe|4aqe]]</div></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4aq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aq8 OCA], [https://pdbe.org/4aq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aq8 RCSB], [https://www.ebi.ac.uk/pdbsum/4aq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aq8 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=4aq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aq8 OCA], [https://pdbe.org/4aq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aq8 RCSB], [https://www.ebi.ac.uk/pdbsum/4aq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aq8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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. [[https://www.uniprot.org/uniprot/PCD15_MOUSE 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.
| + | [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 == |
| - | [[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> [[https://www.uniprot.org/uniprot/PCD15_MOUSE 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.
| + | [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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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Corey, D P]] | + | [[Category: Corey DP]] |
| - | [[Category: Gaudet, R]] | + | [[Category: Gaudet R]] |
| - | [[Category: Sotomayor, M]] | + | [[Category: Sotomayor M]] |
| - | [[Category: Weihofen, W]] | + | [[Category: Weihofen W]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Deafness]]
| + | |
| 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
Hearing and balance use hair cells in the inner ear to transform mechanical stimuli into electrical signals. Mechanical force from sound waves or head movements is conveyed to hair-cell transduction channels by tip links, fine filaments formed by two atypical cadherins known as protocadherin 15 and cadherin 23 (refs 4, 5). These two proteins are involved in inherited deafness and feature long extracellular domains that interact tip-to-tip in a Ca(2+)-dependent manner. However, the molecular architecture of this complex is unknown. Here we combine crystallography, molecular dynamics simulations and binding experiments to characterize the protocadherin 15-cadherin 23 bond. We find a unique cadherin interaction mechanism, in which the two most amino-terminal cadherin repeats (extracellular cadherin repeats 1 and 2) of each protein interact to form an overlapped, antiparallel heterodimer. Simulations predict that this tip-link bond is mechanically strong enough to resist forces in hair cells. In addition, the complex is shown to become unstable in response to Ca(2+) removal owing to increased flexure of Ca(2+)-free cadherin repeats. Finally, we use structures and biochemical measurements to study the molecular mechanisms by which deafness mutations disrupt tip-link function. Overall, our results shed light on the molecular mechanics of hair-cell sensory transduction and on new interaction mechanisms for cadherins, a large protein family implicated in tissue and organ morphogenesis, neural connectivity and cancer.
Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.,Sotomayor M, Weihofen WA, Gaudet R, Corey DP Nature. 2012 Nov 7. doi: 10.1038/nature11590. PMID:23135401[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
- ↑ Sotomayor M, Weihofen WA, Gaudet R, Corey DP. Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction. Nature. 2012 Nov 7. doi: 10.1038/nature11590. PMID:23135401 doi:http://dx.doi.org/10.1038/nature11590
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