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The entry | ==Crystal Structure of Human Protocadherin-15 EC2-3 V250N== | ||
<StructureSection load='6eb5' size='340' side='right'caption='[[6eb5]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6eb5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EB5 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</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=6eb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eb5 OCA], [https://pdbe.org/6eb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eb5 RCSB], [https://www.ebi.ac.uk/pdbsum/6eb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eb5 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PCD15_HUMAN PCD15_HUMAN] Usher syndrome type 1;Autosomal recessive non-syndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PCD15_HUMAN PCD15_HUMAN] Calcium-dependent cell-adhesion protein. Essential for maintenance of normal retinal and cochlear function. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:32963095</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6eb5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cadherin 3D structures|Cadherin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Choudhary D]] | |||
[[Category: Sotomayor M]] | |||
Latest revision as of 09:22, 11 October 2023
Crystal Structure of Human Protocadherin-15 EC2-3 V250NCrystal Structure of Human Protocadherin-15 EC2-3 V250N
Structural highlights
DiseasePCD15_HUMAN Usher syndrome type 1;Autosomal recessive non-syndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionPCD15_HUMAN Calcium-dependent cell-adhesion protein. Essential for maintenance of normal retinal and cochlear function. Publication Abstract from PubMedThe 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 AlsoReferences
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