6cv7: Difference between revisions
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<StructureSection load='6cv7' size='340' side='right'caption='[[6cv7]], [[Resolution|resolution]] 1.69Å' scene=''> | <StructureSection load='6cv7' size='340' side='right'caption='[[6cv7]], [[Resolution|resolution]] 1.69Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cv7]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6cv7]] is a 1 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=6CV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CV7 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>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pcdh15 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pcdh15 ([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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cv7 OCA], [https://pdbe.org/6cv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cv7 RCSB], [https://www.ebi.ac.uk/pdbsum/6cv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cv7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[[ | [[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 == | ||
[[ | [[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;"> | |||
== Publication Abstract from PubMed == | |||
The tip link, a filament formed by protocadherin 15 (PCDH15) and cadherin 23, conveys mechanical force from sound waves and head movement to open hair-cell mechanotransduction channels. Tip-link cadherins are thought to have acquired structural features critical for their role in mechanotransduction. Here, we biophysically and structurally characterize the unusual cis-homodimeric architecture of PCDH15. We show that PCDH15 molecules form double-helical assemblies through cis-dimerization interfaces in the extracellular cadherin EC2-EC3 domain region and in a unique membrane-proximal domain. Electron microscopy studies visualize the cis-dimeric PCDH15 assembly and reveal the PCDH15 extracellular domain as a parallel double helix with cis cross-bridges at the two locations we defined. The helical configuration suggests the potential for elasticity through helix winding and unwinding. Functional studies in hair cells show that mutations that perturb PCDH15 dimerization contacts affect mechanotransduction. Together, these data reveal the cis-dimeric architecture of PCDH15 and show that dimerization is critical for sensing mechanical stimuli. | |||
Mechanotransduction by PCDH15 Relies on a Novel cis-Dimeric Architecture.,Dionne G, Qiu X, Rapp M, Liang X, Zhao B, Peng G, Katsamba PS, Ahlsen G, Rubinstein R, Potter CS, Carragher B, Honig B, Muller U, Shapiro L Neuron. 2018 Aug 8;99(3):480-492.e5. doi: 10.1016/j.neuron.2018.07.006. Epub 2018, Jul 26. PMID:30057206<ref>PMID:30057206</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6cv7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cadherin 3D structures|Cadherin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 10:39, 25 June 2021
Mouse Protocadherin-15 Extracellular Cadherin Domains 1 through 3Mouse Protocadherin-15 Extracellular Cadherin Domains 1 through 3
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 PubMedThe tip link, a filament formed by protocadherin 15 (PCDH15) and cadherin 23, conveys mechanical force from sound waves and head movement to open hair-cell mechanotransduction channels. Tip-link cadherins are thought to have acquired structural features critical for their role in mechanotransduction. Here, we biophysically and structurally characterize the unusual cis-homodimeric architecture of PCDH15. We show that PCDH15 molecules form double-helical assemblies through cis-dimerization interfaces in the extracellular cadherin EC2-EC3 domain region and in a unique membrane-proximal domain. Electron microscopy studies visualize the cis-dimeric PCDH15 assembly and reveal the PCDH15 extracellular domain as a parallel double helix with cis cross-bridges at the two locations we defined. The helical configuration suggests the potential for elasticity through helix winding and unwinding. Functional studies in hair cells show that mutations that perturb PCDH15 dimerization contacts affect mechanotransduction. Together, these data reveal the cis-dimeric architecture of PCDH15 and show that dimerization is critical for sensing mechanical stimuli. Mechanotransduction by PCDH15 Relies on a Novel cis-Dimeric Architecture.,Dionne G, Qiu X, Rapp M, Liang X, Zhao B, Peng G, Katsamba PS, Ahlsen G, Rubinstein R, Potter CS, Carragher B, Honig B, Muller U, Shapiro L Neuron. 2018 Aug 8;99(3):480-492.e5. doi: 10.1016/j.neuron.2018.07.006. Epub 2018, Jul 26. PMID:30057206[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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