2kq6

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{{Seed}}
 
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[[Image:2kq6.png|left|200px]]
 
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==The structure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity==
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The line below this paragraph, containing "STRUCTURE_2kq6", creates the "Structure Box" on the page.
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<StructureSection load='2kq6' size='340' side='right'caption='[[2kq6]]' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2kq6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KQ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KQ6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kq6 OCA], [https://pdbe.org/2kq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kq6 RCSB], [https://www.ebi.ac.uk/pdbsum/2kq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kq6 ProSAT]</span></td></tr>
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{{STRUCTURE_2kq6| PDB=2kq6 | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PKD2_HUMAN PKD2_HUMAN] Defects in PKD2 are the cause of polycystic kidney disease 2 (PKD2) [MIM:[https://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>
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== Function ==
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[https://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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/2kq6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/main_output.php?pdb_ID=2kq6 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The C-terminal cytoplasmic tail of polycystin-2 (PC2/TRPP2), a Ca(2+)-permeable channel, is frequently mutated or truncated in autosomal dominant polycystic kidney disease. We have previously shown that this tail consists of three functional regions: an EF-hand domain (PC2-EF, 720-797), a flexible linker (798-827), and an oligomeric coiled coil domain (828-895). We found that PC2-EF binds Ca(2+) at a single site and undergoes Ca(2+)-dependent conformational changes, suggesting it is an essential element of Ca(2+)-sensitive regulation of PC2 activity. Here we describe the NMR structure and dynamics of Ca(2+)-bound PC2-EF. Human PC2-EF contains a divergent non-Ca(2+)-binding helix-loop-helix (HLH) motif packed against a canonical Ca(2+)-binding EF-hand motif. This HLH motif may have evolved from a canonical EF-hand found in invertebrate PC2 homologs. Temperature-dependent steady-state NOE experiments and NMR R(1) and R(2) relaxation rates correlate with increased molecular motion in the EF-hand, possibly due to exchange between apo and Ca(2+)-bound states, consistent with a role for PC2-EF as a Ca(2+)-sensitive regulator. Structure-based sequence conservation analysis reveals a conserved hydrophobic surface in the same region, which may mediate Ca(2+)-dependent protein interactions. We propose that Ca(2+)-sensing by PC2-EF is responsible for the cooperative nature of PC2 channel activation and inhibition. Based on our results, we present a mechanism of regulation of the Ca(2+) dependence of PC2 channel activity by PC2-EF.
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===The structure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity===
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Structure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity.,Petri ET, Celic A, Kennedy SD, Ehrlich BE, Boggon TJ, Hodsdon ME Proc Natl Acad Sci U S A. 2010 May 18;107(20):9176-81. Epub 2010 May 3. PMID:20439752<ref>PMID:20439752</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2kq6" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 20439752 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20439752}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Polycystic kidney disease, adult, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173910 173910]]
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==About this Structure==
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2KQ6 is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KQ6 OCA].
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==Reference==
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<ref group="xtra">PMID:20439752</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Boggon, T J.]]
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[[Category: Large Structures]]
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[[Category: Celic, A.]]
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[[Category: Boggon TJ]]
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[[Category: Ehrlich, B E.]]
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[[Category: Celic A]]
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[[Category: Hodsdon, M E.]]
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[[Category: Ehrlich BE]]
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[[Category: Kennedy, S D.]]
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[[Category: Hodsdon ME]]
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[[Category: Petri, E T.]]
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[[Category: Kennedy SD]]
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[[Category: Calcium]]
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[[Category: Petri ET]]
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[[Category: Coiled coil]]
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[[Category: Disease mutation]]
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[[Category: Glycoprotein]]
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[[Category: Ion transport]]
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[[Category: Ionic channel]]
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[[Category: Membrane]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Protein x]]
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[[Category: Transmembrane]]
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[[Category: Transport]]
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[[Category: Transport protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 10 10:50:32 2010''
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Current revision

The structure of the EF-hand domain of polycystin-2 suggests a mechanism for Ca2+-dependent regulation of polycystin-2 channel activity

PDB ID 2kq6

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