3hrn: Difference between revisions
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==crystal structure of a C-terminal coiled coil domain of Transient receptor potential (TRP) channel subfamily P member 2 (TRPP2, polycystic kidney disease 2)== | |||
<StructureSection load='3hrn' size='340' side='right' caption='[[3hrn]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3hrn]] is a 1 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=3HRN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HRN FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hro|3hro]]</td></tr> | ||
[[http://www.uniprot.org/uniprot/PKD2_HUMAN PKD2_HUMAN]] Defects in PKD2 are the cause of polycystic kidney disease 2 (PKD2) [MIM:[http://omim.org/entry/613095 613095]]. PKD2 is a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy.<ref>PMID:9326320</ref><ref>PMID:10541293</ref><ref>PMID:10411676</ref><ref>PMID:10835625</ref><ref>PMID:11968093</ref><ref>PMID:12707387</ref><ref>PMID:14993477</ref><ref>PMID:15772804</ref><ref>PMID:21115670</ref> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3hrn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hrn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hrn RCSB], [http://www.ebi.ac.uk/pdbsum/3hrn PDBsum]</span></td></tr> | |||
==Function== | </table> | ||
== Disease == | |||
[[http://www.uniprot.org/uniprot/PKD2_HUMAN PKD2_HUMAN]] Defects in PKD2 are the cause of polycystic kidney disease 2 (PKD2) [MIM:[http://omim.org/entry/613095 613095]]. PKD2 is a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy.<ref>PMID:9326320</ref> <ref>PMID:10541293</ref> <ref>PMID:10411676</ref> <ref>PMID:10835625</ref> <ref>PMID:11968093</ref> <ref>PMID:12707387</ref> <ref>PMID:14993477</ref> <ref>PMID:15772804</ref> <ref>PMID:21115670</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/PKD2_HUMAN PKD2_HUMAN]] Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis (By similarity). Acts as a regulator of cilium length, together with PKD1 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). Functions as a calcium permeable cation channel. | [[http://www.uniprot.org/uniprot/PKD2_HUMAN PKD2_HUMAN]] Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis (By similarity). Acts as a regulator of cilium length, together with PKD1 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). Functions as a calcium permeable cation channel. | ||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/3hrn_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mutations in PKD1 and TRPP2 account for nearly all cases of autosomal dominant polycystic kidney disease (ADPKD). These 2 proteins form a receptor/ion channel complex on the cell surface. Using a combination of biochemistry, crystallography, and a single-molecule method to determine the subunit composition of proteins in the plasma membrane of live cells, we find that this complex contains 3 TRPP2 and 1 PKD1. A newly identified coiled-coil domain in the C terminus of TRPP2 is critical for the formation of this complex. This coiled-coil domain forms a homotrimer, in both solution and crystal structure, and binds to a single coiled-coil domain in the C terminus of PKD1. Mutations that disrupt the TRPP2 coiled-coil domain trimer abolish the assembly of both the full-length TRPP2 trimer and the TRPP2/PKD1 complex and diminish the surface expression of both proteins. These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations. | |||
Structural and molecular basis of the assembly of the TRPP2/PKD1 complex.,Yu Y, Ulbrich MH, Li MH, Buraei Z, Chen XZ, Ong AC, Tong L, Isacoff EY, Yang J Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11558-63. Epub 2009 Jun 25. PMID:19556541<ref>PMID:19556541</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Buraei, Z | [[Category: Buraei, Z]] | ||
[[Category: Chen, X Z | [[Category: Chen, X Z]] | ||
[[Category: Isacoff, E Y | [[Category: Isacoff, E Y]] | ||
[[Category: Li, M H | [[Category: Li, M H]] | ||
[[Category: Ong, A C.M | [[Category: Ong, A C.M]] | ||
[[Category: Tong, L | [[Category: Tong, L]] | ||
[[Category: Ulbrich, M H | [[Category: Ulbrich, M H]] | ||
[[Category: Yang, J | [[Category: Yang, J]] | ||
[[Category: Yu, Y | [[Category: Yu, Y]] | ||
[[Category: Disease mutation]] | [[Category: Disease mutation]] | ||
[[Category: Glycoprotein]] | [[Category: Glycoprotein]] | ||
