6fdd: Difference between revisions
New page: '''Unreleased structure''' The entry 6fdd is ON HOLD until Paper Publication Authors: Delhommel, F., Cordier, F., Saul, F., Haouz, A., Wolff, N. Description: Crystal Structure of the H... |
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The | ==Crystal Structure of the HHD2 Domain of Whirlin== | ||
<StructureSection load='6fdd' size='340' side='right'caption='[[6fdd]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6fdd]] is a 6 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=6FDD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FDD 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]] 1.75Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6fdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fdd OCA], [https://pdbe.org/6fdd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fdd RCSB], [https://www.ebi.ac.uk/pdbsum/6fdd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fdd ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/WHRN_MOUSE WHRN_MOUSE] Defects in Whrn are the cause of the phenotype whirler (wi). Mutants are characterized by deafness due to malformation of the cochlear inner and outer hair cells and by circling behavior. Stereocilia are shorter and wider than in wild-type animals and there is a decrease in the number of actin filaments in inner and outer hair cells. The number of outer hair cell stereocilia is reduced with increased spacing between them.<ref>PMID:12124769</ref> <ref>PMID:12833159</ref> <ref>PMID:17326148</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/WHRN_MOUSE WHRN_MOUSE] Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear.<ref>PMID:15590699</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Whirlin is a protein essential to sensory neurons. Its defects are responsible for non-syndromic deafness or for the Usher syndrome, a condition associating congenital deafness and progressive blindness. This large multidomain scaffolding protein is expressed in three isoforms with different functions and localizations in stereocilia bundles of hearing hair cells or in the connector cilia of photoreceptor cells. The HHD2 domain of whirlin is the only domain shared by all isoforms, but its function remains unknown. In this article, we report its crystal structure in two distinct conformations, a monomeric five-helix bundle, similar to the known structure of other HHD domains, and a three-helix bundle organized as a swapped dimer. Most of the hydrophobic contacts and electrostatic interactions that maintain the globular monomeric form are conserved at the protomer interface of the dimer. NMR experiments revealed that the five-helix conformation is predominant in solution, but exhibits increased dynamics on one face encompassing the hinge loops. Using NMR and SAXS, we also show that HHD2 does not interact with its preceding domains. Our findings suggest that structural plasticity might play a role in the function of the HHD2 domain. This article is protected by copyright. All rights reserved. | |||
Structural plasticity of the HHD2 domain of whirlin.,Delhommel F, Cordier F, Saul F, Chataigner L, Haouz A, Wolff N FEBS J. 2018 Jul 27. doi: 10.1111/febs.14614. PMID:30053338<ref>PMID:30053338</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6fdd" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Delhommel | <references/> | ||
[[Category: Haouz | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Cordier F]] | |||
[[Category: Delhommel F]] | |||
[[Category: Haouz A]] | |||
[[Category: Saul F]] | |||
[[Category: Wolff N]] | |||
Latest revision as of 12:55, 23 October 2024
Crystal Structure of the HHD2 Domain of WhirlinCrystal Structure of the HHD2 Domain of Whirlin
Structural highlights
DiseaseWHRN_MOUSE Defects in Whrn are the cause of the phenotype whirler (wi). Mutants are characterized by deafness due to malformation of the cochlear inner and outer hair cells and by circling behavior. Stereocilia are shorter and wider than in wild-type animals and there is a decrease in the number of actin filaments in inner and outer hair cells. The number of outer hair cell stereocilia is reduced with increased spacing between them.[1] [2] [3] FunctionWHRN_MOUSE Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear.[4] Publication Abstract from PubMedWhirlin is a protein essential to sensory neurons. Its defects are responsible for non-syndromic deafness or for the Usher syndrome, a condition associating congenital deafness and progressive blindness. This large multidomain scaffolding protein is expressed in three isoforms with different functions and localizations in stereocilia bundles of hearing hair cells or in the connector cilia of photoreceptor cells. The HHD2 domain of whirlin is the only domain shared by all isoforms, but its function remains unknown. In this article, we report its crystal structure in two distinct conformations, a monomeric five-helix bundle, similar to the known structure of other HHD domains, and a three-helix bundle organized as a swapped dimer. Most of the hydrophobic contacts and electrostatic interactions that maintain the globular monomeric form are conserved at the protomer interface of the dimer. NMR experiments revealed that the five-helix conformation is predominant in solution, but exhibits increased dynamics on one face encompassing the hinge loops. Using NMR and SAXS, we also show that HHD2 does not interact with its preceding domains. Our findings suggest that structural plasticity might play a role in the function of the HHD2 domain. This article is protected by copyright. All rights reserved. Structural plasticity of the HHD2 domain of whirlin.,Delhommel F, Cordier F, Saul F, Chataigner L, Haouz A, Wolff N FEBS J. 2018 Jul 27. doi: 10.1111/febs.14614. PMID:30053338[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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