6t9o: Difference between revisions
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==CryoEM structure of human polycystin-2/PKD2 in UDM supplemented with PI(3,5)P2== | ==CryoEM structure of human polycystin-2/PKD2 in UDM supplemented with PI(3,5)P2== | ||
< | <SX load='6t9o' size='340' side='right' viewer='molstar' caption='[[6t9o]], [[Resolution|resolution]] 3.39Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6t9o]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T9O OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6t9o]] 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=6T9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T9O FirstGlance]. <br> | ||
</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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UMQ:UNDECYL-MALTOSIDE'>UMQ</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.39Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UMQ:UNDECYL-MALTOSIDE'>UMQ</scene></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=6t9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t9o OCA], [https://pdbe.org/6t9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t9o RCSB], [https://www.ebi.ac.uk/pdbsum/6t9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t9o ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [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 == | ||
[ | [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. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Polycystin-2 (PC2) is a transient receptor potential (TRP) channel present in ciliary membranes of the kidney. PC2 shares a transmembrane fold with other TRP channels, in addition to an extracellular domain found in TRPP and TRPML channels. Using molecular dynamics (MD) simulations and cryoelectron microscopy we identify and characterize PIP2 and cholesterol interactions with PC2. PC2 is revealed to have a PIP binding site close to the equivalent vanilloid/lipid binding site in the TRPV1 channel. A 3.0-A structure reveals a binding site for cholesterol on PC2. Cholesterol interactions with the channel at this site are characterized by MD simulations. The two classes of lipid binding sites are compared with sites observed in other TRPs and in Kv channels. These findings suggest PC2, in common with other ion channels, may be modulated by both PIPs and cholesterol, and position PC2 within an emerging model of the roles of lipids in the regulation and organization of ciliary membranes. | |||
Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2.,Wang Q, Corey RA, Hedger G, Aryal P, Grieben M, Nasrallah C, Baronina A, Pike ACW, Shi J, Carpenter EP, Sansom MSP Structure. 2019 Nov 27. pii: S0969-2126(19)30389-2. doi:, 10.1016/j.str.2019.11.005. PMID:31806353<ref>PMID:31806353</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6t9o" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</ | </SX> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith CH]] | ||
[[Category: Baronina | [[Category: Baronina A]] | ||
[[Category: Bountra | [[Category: Bountra C]] | ||
[[Category: Carpenter | [[Category: Carpenter EP]] | ||
[[Category: Edwards | [[Category: Edwards AM]] | ||
[[Category: Grieben | [[Category: Grieben M]] | ||
[[Category: Nasrallah | [[Category: Nasrallah C]] | ||
[[Category: Pike | [[Category: Pike ACW]] | ||
[[Category: Shintre C]] | |||
[[Category: Shintre | [[Category: Wang Q]] | ||
[[Category: Wang | |||