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| | <SX load='6c14' size='340' side='right' viewer='molstar' caption='[[6c14]], [[Resolution|resolution]] 4.50Å' scene=''> | | <SX load='6c14' size='340' side='right' viewer='molstar' caption='[[6c14]], [[Resolution|resolution]] 4.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6c14]] 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=6C14 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C14 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6c14]] 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=6C14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C14 FirstGlance]. <br> |
| - | </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]), Lhfpl5, Tmhs ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.5Å</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=6c14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c14 OCA], [http://pdbe.org/6c14 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c14 RCSB], [http://www.ebi.ac.uk/pdbsum/6c14 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c14 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=6c14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c14 OCA], [https://pdbe.org/6c14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c14 RCSB], [https://www.ebi.ac.uk/pdbsum/6c14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c14 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. [[http://www.uniprot.org/uniprot/LHPL5_MOUSE LHPL5_MOUSE]] Defects in Lhfpl5 are the cause of the hurry-scurry (hscy) phenotype which is characterized by rapid circling behavior, frequent shaking of head from side to side, deafness and vestibular dysfunction.<ref>PMID:15905332</ref> | + | [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. [[http://www.uniprot.org/uniprot/LHPL5_MOUSE LHPL5_MOUSE]] In the inner ear, may be a component of the hair cell's mechanotransduction machinery that functionally couples PCDH15 to the transduction channel. Regulates transducer channel conductance and is required for fast channel adaptation.<ref>PMID:15905332</ref> <ref>PMID:23217710</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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Elferich, J]] | + | [[Category: Elferich J]] |
| - | [[Category: Ge, J]] | + | [[Category: Ge J]] |
| - | [[Category: Gouaux, E]] | + | [[Category: Gouaux E]] |
| - | [[Category: Hair cell]]
| + | |
| - | [[Category: Hearing]]
| + | |
| - | [[Category: Lhfpl5]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Metal transport]]
| + | |
| - | [[Category: Pcdh15]]
| + | |
| - | [[Category: Protocadherin]]
| + | |
| - | [[Category: Tip link]]
| + | |
| - | [[Category: Tmh]]
| + | |
| 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
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
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