4dx1

From Proteopedia

(Difference between revisions)

Revision as of 02:52, 11 December 2016

Crystal structure of the human TRPV4 ankyrin repeat domain

Structural highlights

4dx1 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4dx2
Gene:	TRPV4, VRL2, VROAC (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TRPV4_HUMAN] Spondylometaphyseal dysplasia, Kozlowski type;Familial digital arthropathy-brachydactyly;Autosomal dominant brachyolmia;Autosomal dominant congenital benign spinal muscular atrophy;Parastremmatic dwarfism;Spondyloepiphyseal dysplasia, Maroteaux type;Autosomal dominant Charcot-Marie-Tooth disease type 2C;Metatropic dysplasia. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TRPV4_HUMAN] Non-selective calcium permeant cation channel probably involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by low pH, citrate and phorbol esters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers. Acts as a regulator of intracellular Ca(2+) in synoviocytes. Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The TRPV4 calcium-permeable cation channel plays important physiological roles in osmosensation, mechanosensation, cell barrier formation, and bone homeostasis. Recent studies reported that mutations in TRPV4, including some in its ankyrin repeat domain (ARD), are associated with human inherited diseases including neuropathies and skeletal dysplasias, probably due to increased constitutive activity of the channel. TRPV4 activity is regulated by the binding of calmodulin and small molecules such as ATP to the ARD in its cytoplasmic N-terminus. We determined structures of ATP-free and -bound forms of human TRPV4-ARD and compared them with available TRPV-ARD structures. The third inter-repeat loop region (Finger 3 loop) is flexible and may act as a switch to regulate the channel activity. Comparisons of TRPV-ARD structures also suggest an evolutionary link between ARD structure and ATP binding ability. Thermal stability analyses and molecular dynamics (MD) simulations suggest that ATP increases stability in TRPV-ARDs that can bind ATP. Biochemical analyses of a large panel of TRPV4-ARD mutations associated with human inherited diseases showed that some impaired thermal stability while others reduced ATP binding ability, suggesting molecular mechanisms for the diseases.

Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.,Inada H, Procko E, Sotomayor M, Gaudet R Biochemistry. 2012 Jun 15. PMID:22702953^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat Cell Biol. 2000 Oct;2(10):695-702. PMID:11025659 doi:http://dx.doi.org/10.1038/35036318
↑ Strotmann R, Schultz G, Plant TD. Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site. J Biol Chem. 2003 Jul 18;278(29):26541-9. Epub 2003 Apr 30. PMID:12724311 doi:http://dx.doi.org/10.1074/jbc.M302590200
↑ Itoh Y, Hatano N, Hayashi H, Onozaki K, Miyazawa K, Muraki K. An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes. Am J Physiol Cell Physiol. 2009 Nov;297(5):C1082-90. doi:, 10.1152/ajpcell.00204.2009. Epub 2009 Sep 16. PMID:19759329 doi:http://dx.doi.org/10.1152/ajpcell.00204.2009
↑ Inada H, Procko E, Sotomayor M, Gaudet R. Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel. Biochemistry. 2012 Jun 15. PMID:22702953 doi:10.1021/bi300279b

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dx1"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human TRPV4 ankyrin repeat domain==
 <StructureSection load='4dx1' size='340' side='right' caption='[[4dx1]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4dx1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DX1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dx1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DX1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DX1 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dx2|4dx2]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPV4, VRL2, VROAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPV4, VRL2, VROAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4dx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dx1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dx1 RCSB], [http://www.ebi.ac.uk/pdbsum/4dx1 PDBsum]</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=4dx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dx1 OCA], [http://pdbe.org/4dx1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dx1 RCSB], [http://www.ebi.ac.uk/pdbsum/4dx1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dx1 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4dx1" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Gaudet, R]]
 [[Category: Inada, H]]

4dx1

From Proteopedia

Revision as of 02:52, 11 December 2016

Crystal structure of the human TRPV4 ankyrin repeat domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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