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| | ==Crystal structure of the chicken TRPV4 ankyrin repeat domain== | | ==Crystal structure of the chicken TRPV4 ankyrin repeat domain== |
| - | <StructureSection load='3jxj' size='340' side='right' caption='[[3jxj]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3jxj' size='340' side='right'caption='[[3jxj]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3jxj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JXJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JXJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3jxj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JXJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JXJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2pnn|2pnn]], [[2etb|2etb]], [[2rfa|2rfa]], [[3jxi|3jxi]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPV4, VR-OAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</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=3jxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jxj OCA], [https://pdbe.org/3jxj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jxj RCSB], [https://www.ebi.ac.uk/pdbsum/3jxj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jxj 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=3jxj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jxj OCA], [http://pdbe.org/3jxj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jxj RCSB], [http://www.ebi.ac.uk/pdbsum/3jxj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jxj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TRPV4_CHICK TRPV4_CHICK] Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11081638). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:11081638). Also activated by phorbol esters (PubMed:19864432). Channel activity seems to be regulated by a calmodulin-dependent mechanism (By similarity).[UniProtKB:Q9HBA0]<ref>PMID:11081638</ref> <ref>PMID:19864432</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jx/3jxj_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jx/3jxj_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3jxj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3jxj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chick]] | + | [[Category: Gallus gallus]] |
| - | [[Category: Choo, S S]] | + | [[Category: Large Structures]] |
| - | [[Category: Gaudet, R]] | + | [[Category: Choo SS]] |
| - | [[Category: Phelps, C B]] | + | [[Category: Gaudet R]] |
| - | [[Category: Ank repeat]] | + | [[Category: Phelps CB]] |
| - | [[Category: Ankyrin repeat]]
| + | |
| - | [[Category: Ion transport]]
| + | |
| - | [[Category: Ionic channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Transport]]
| + | |
| Structural highlights
Function
TRPV4_CHICK Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11081638). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:11081638). Also activated by phorbol esters (PubMed:19864432). Channel activity seems to be regulated by a calmodulin-dependent mechanism (By similarity).[UniProtKB:Q9HBA0][1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy characterized by limb, diaphragm and laryngeal muscle weakness. Two unrelated families with CMT2C showed significant linkage to chromosome 12q24.11. We sequenced all genes in this region and identified two heterozygous missense mutations in the TRPV4 gene, C805T and G806A, resulting in the amino acid substitutions R269C and R269H. TRPV4 is a well-known member of the TRP superfamily of cation channels. In TRPV4-transfected cells, the CMT2C mutations caused marked cellular toxicity and increased constitutive and activated channel currents. Mutations in TRPV4 were previously associated with skeletal dysplasias. Our findings indicate that TRPV4 mutations can also cause a degenerative disorder of the peripheral nerves. The CMT2C-associated mutations lie in a distinct region of the TRPV4 ankyrin repeats, suggesting that this phenotypic variability may be due to differential effects on regulatory protein-protein interactions.
Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.,Landoure G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ Nat Genet. 2010 Feb;42(2):170-4. Epub 2009 Dec 27. PMID:20037586[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liedtke W, Choe Y, Martí-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell. 2000 Oct 27;103(3):525-35. PMID:11081638 doi:10.1016/s0092-8674(00)00143-4
- ↑ Phelps CB, Wang RR, Choo SS, Gaudet R. Differential regulation of TRPV1, TRPV3, and TRPV4 sensitivity through a conserved binding site on the ankyrin repeat domain. J Biol Chem. 2010 Jan 1;285(1):731-40. PMID:19864432 doi:10.1074/jbc.M109.052548
- ↑ Landoure G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nat Genet. 2010 Feb;42(2):170-4. Epub 2009 Dec 27. PMID:20037586 doi:10.1038/ng.512
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