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| | <StructureSection load='6n22' size='340' side='right'caption='[[6n22]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6n22' size='340' side='right'caption='[[6n22]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n22]] is a 1 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=6N22 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6N22 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n22]] is a 1 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=6N22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N22 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]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pcdh15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6n22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n22 OCA], [http://pdbe.org/6n22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n22 RCSB], [http://www.ebi.ac.uk/pdbsum/6n22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n22 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=6n22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n22 OCA], [https://pdbe.org/6n22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n22 RCSB], [https://www.ebi.ac.uk/pdbsum/6n22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n22 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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/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. |
| | == Function == | | == Function == |
| - | [[http://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/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. |
| | <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 6n22" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6n22" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cadherin 3D structures|Cadherin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Narui, Y]] | + | [[Category: Narui Y]] |
| - | [[Category: Sotomayor, M]] | + | [[Category: Sotomayor M]] |
| - | [[Category: Calcium binding protein]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Hearing]]
| + | |
| - | [[Category: Mechanotransduction]]
| + | |
| - | [[Category: Stereocilia]]
| + | |
| - | [[Category: Tip link]]
| + | |
| Structural highlights
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
The vertebrate inner ear, responsible for hearing and balance, is able to sense minute mechanical stimuli originating from an extraordinarily broad range of sound frequencies and intensities or from head movements. Integral to these processes is the tip-link protein complex, which conveys force to open the inner-ear transduction channels that mediate sensory perception. Protocadherin-15 and cadherin-23, two atypically large cadherins with 11 and 27 extracellular cadherin (EC) repeats, are involved in deafness and balance disorders and assemble as parallel homodimers that interact to form the tip link. Here we report the X-ray crystal structure of a protocadherin-15 + cadherin-23 heterotetrameric complex at 2.9-A resolution, depicting a parallel homodimer of protocadherin-15 EC1-3 molecules forming an antiparallel complex with two cadherin-23 EC1-2 molecules. In addition, we report structures for 10 protocadherin-15 fragments used to build complete high-resolution models of the monomeric protocadherin-15 ectodomain. Molecular dynamics simulations and validated crystal contacts are used to propose models for the complete extracellular protocadherin-15 parallel homodimer and the tip-link bond. Steered molecular dynamics simulations of these models suggest conditions in which a structurally diverse and multimodal protocadherin-15 ectodomain can act as a stiff or soft gating spring. These results reveal the structural determinants of tip-link-mediated inner-ear sensory perception and elucidate protocadherin-15's structural and adhesive properties relevant in disease.
Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception.,Choudhary D, Narui Y, Neel BL, Wimalasena LN, Klanseck CF, De-la-Torre P, Chen C, Araya-Secchi R, Tamilselvan E, Sotomayor M Proc Natl Acad Sci U S A. 2020 Sep 22. pii: 1920444117. doi:, 10.1073/pnas.1920444117. PMID:32963095[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Choudhary D, Narui Y, Neel BL, Wimalasena LN, Klanseck CF, De-la-Torre P, Chen C, Araya-Secchi R, Tamilselvan E, Sotomayor M. Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception. Proc Natl Acad Sci U S A. 2020 Sep 22. pii: 1920444117. doi:, 10.1073/pnas.1920444117. PMID:32963095 doi:http://dx.doi.org/10.1073/pnas.1920444117
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