5mkf

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==cryoEM Structure of Polycystin-2 in complex with calcium and lipids==
==cryoEM Structure of Polycystin-2 in complex with calcium and lipids==
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<StructureSection load='5mkf' size='340' side='right' caption='[[5mkf]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
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<SX load='5mkf' size='340' side='right' viewer='molstar' caption='[[5mkf]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5mkf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MKF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MKF FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5mkf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MKF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CHS:4-AMINO-5-CYCLOHEXYL-3-HYDROXY-PENTANOIC+ACID'>CHS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=PX6:1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE'>PX6</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2&#8491;</td></tr>
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<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=5mkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mkf OCA], [http://pdbe.org/5mkf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mkf RCSB], [http://www.ebi.ac.uk/pdbsum/5mkf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mkf ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CHS:4-AMINO-5-CYCLOHEXYL-3-HYDROXY-PENTANOIC+ACID'>CHS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=PX6:1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE'>PX6</scene></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=5mkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mkf OCA], [https://pdbe.org/5mkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mkf RCSB], [https://www.ebi.ac.uk/pdbsum/5mkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mkf ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[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>
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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>
== Function ==
== Function ==
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[[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.
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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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca2+ signaling pathways. Malfunctioning Ca2+ regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here we report two cryo-EM structures of distinct channel states of full-length human PC2 in complex with lipids and cations. The structures reveal conformational differences in the selectivity filter and in the large exoplasmic domain (TOP domain), which displays differing N-glycosylation. The more open structure has one cation bound below the selectivity filter (single-ion mode, PC2SI), whereas multiple cations are bound along the translocation pathway in the second structure (multi-ion mode, PC2MI). Ca2+ binding at the entrance of the selectivity filter suggests Ca2+ blockage in PC2MI, and we observed density for the Ca2+-sensing C-terminal EF hand in the unblocked PC2SI state. The states show altered interactions of lipids with the pore loop and TOP domain, thus reflecting the functional diversity of PC2 at different locations, owing to different membrane compositions.
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Molecular insights into lipid-assisted Ca2+ regulation of the TRP channel Polycystin-2.,Wilkes M, Madej MG, Kreuter L, Rhinow D, Heinz V, De Sanctis S, Ruppel S, Richter RM, Joos F, Grieben M, Pike AC, Huiskonen JT, Carpenter EP, Kuhlbrandt W, Witzgall R, Ziegler C Nat Struct Mol Biol. 2017 Jan 16. doi: 10.1038/nsmb.3357. PMID:28092368<ref>PMID:28092368</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>
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<div class="pdbe-citations 5mkf" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
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</StructureSection>
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</SX>
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[[Category: Madej, M G]]
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[[Category: Homo sapiens]]
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[[Category: Wilkes, M]]
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[[Category: Large Structures]]
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[[Category: Ziegler, C]]
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[[Category: Madej MG]]
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[[Category: Ca2+ signaling]]
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[[Category: Wilkes M]]
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[[Category: Cryoem]]
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[[Category: Ziegler C]]
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[[Category: Membrane protein structure]]
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[[Category: Polycystin-2]]
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[[Category: Transport protein]]
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[[Category: Trp channel]]
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Current revision

cryoEM Structure of Polycystin-2 in complex with calcium and lipids

5mkf, resolution 4.20Å

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