5tfl: Difference between revisions
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<StructureSection load='5tfl' size='340' side='right' caption='[[5tfl]], [[Resolution|resolution]] 3.56Å' scene=''> | <StructureSection load='5tfl' size='340' side='right' caption='[[5tfl]], [[Resolution|resolution]] 3.56Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5tfl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TFL FirstGlance]. <br> | <table><tr><td colspan='2'>[[5tfl]] is a 2 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=5TFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TFL 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>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tfm|5tfm]], [[5tfk|5tfk]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tfm|5tfm]], [[5tfk|5tfk]]</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='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=5tfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tfl OCA], [http://pdbe.org/5tfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tfl RCSB], [http://www.ebi.ac.uk/pdbsum/5tfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tfl ProSAT]</span></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=5tfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tfl OCA], [http://pdbe.org/5tfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tfl RCSB], [http://www.ebi.ac.uk/pdbsum/5tfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tfl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== 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> | [[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> | ||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:30033219</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5tfl" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cadherin|Cadherin]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Jaiganesh, A]] | [[Category: Jaiganesh, A]] | ||
[[Category: Sotomayor, M]] | [[Category: Sotomayor, M]] | ||
Revision as of 22:01, 1 August 2018
Crystal Structure of Mouse Cadherin-23 EC7+8Crystal Structure of Mouse Cadherin-23 EC7+8
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 PubMedCadherin-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 AlsoReferences
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