|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of the HHD2 Domain of Whirlin== | | ==Crystal Structure of the HHD2 Domain of Whirlin== |
| - | <StructureSection load='6fdd' size='340' side='right' caption='[[6fdd]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='6fdd' size='340' side='right'caption='[[6fdd]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6fdd]] is a 6 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=6FDD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FDD FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fde|6fde]]</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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Whrn, Dfnb31, Kiaa1526 ([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=6fdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fdd OCA], [http://pdbe.org/6fdd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fdd RCSB], [http://www.ebi.ac.uk/pdbsum/6fdd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fdd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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> | + | [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 == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Cordier, F]] | + | [[Category: Mus musculus]] |
| - | [[Category: Delhommel, F]] | + | [[Category: Cordier F]] |
| - | [[Category: Haouz, A]] | + | [[Category: Delhommel F]] |
| - | [[Category: Saul, F]] | + | [[Category: Haouz A]] |
| - | [[Category: Wolff, N]] | + | [[Category: Saul F]] |
| - | [[Category: Deafness]]
| + | [[Category: Wolff N]] |
| - | [[Category: Hearing]]
| + | |
| - | [[Category: Scaffold protein]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Usher syndrome]]
| + | |
| Structural highlights
Disease
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.[1] [2] [3]
Function
WHRN_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 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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Holme RH, Kiernan BW, Brown SD, Steel KP. Elongation of hair cell stereocilia is defective in the mouse mutant whirler. J Comp Neurol. 2002 Aug 12;450(1):94-102. PMID:12124769 doi:http://dx.doi.org/10.1002/cne.10301
- ↑ Mburu P, Mustapha M, Varela A, Weil D, El-Amraoui A, Holme RH, Rump A, Hardisty RE, Blanchard S, Coimbra RS, Perfettini I, Parkinson N, Mallon AM, Glenister P, Rogers MJ, Paige AJ, Moir L, Clay J, Rosenthal A, Liu XZ, Blanco G, Steel KP, Petit C, Brown SD. Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. Nat Genet. 2003 Aug;34(4):421-8. PMID:12833159 doi:10.1038/ng1208
- ↑ Mogensen MM, Rzadzinska A, Steel KP. The deaf mouse mutant whirler suggests a role for whirlin in actin filament dynamics and stereocilia development. Cell Motil Cytoskeleton. 2007 Jul;64(7):496-508. PMID:17326148 doi:http://dx.doi.org/10.1002/cm.20199
- ↑ Kikkawa Y, Mburu P, Morse S, Kominami R, Townsend S, Brown SD. Mutant analysis reveals whirlin as a dynamic organizer in the growing hair cell stereocilium. Hum Mol Genet. 2005 Feb 1;14(3):391-400. Epub 2004 Dec 8. PMID:15590699 doi:http://dx.doi.org/ddi035
- ↑ Delhommel F, Cordier F, Saul F, Chataigner L, Haouz A, Wolff N. Structural plasticity of the HHD2 domain of whirlin. FEBS J. 2018 Jul 27. doi: 10.1111/febs.14614. PMID:30053338 doi:http://dx.doi.org/10.1111/febs.14614
|
