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| | <SX load='6dmr' size='340' side='right' viewer='molstar' caption='[[6dmr]], [[Resolution|resolution]] 3.90Å' scene=''> | | <SX load='6dmr' size='340' side='right' viewer='molstar' caption='[[6dmr]], [[Resolution|resolution]] 3.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dmr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DMR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DMR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dmr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DMR FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpv5, Ecac1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</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]] 3.9Å</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=6dmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dmr OCA], [http://pdbe.org/6dmr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dmr RCSB], [http://www.ebi.ac.uk/pdbsum/6dmr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dmr ProSAT]</span></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=6dmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dmr OCA], [https://pdbe.org/6dmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dmr RCSB], [https://www.ebi.ac.uk/pdbsum/6dmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dmr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRPV5_RABIT TRPV5_RABIT]] Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5]<ref>PMID:10085067</ref> <ref>PMID:11035011</ref> <ref>PMID:12574114</ref> | + | [https://www.uniprot.org/uniprot/TRPV5_RABIT TRPV5_RABIT] Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12574114). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).[UniProtKB:P69744][UniProtKB:Q9NQA5]<ref>PMID:10085067</ref> <ref>PMID:11035011</ref> <ref>PMID:12574114</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-pi interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery.
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| - | Structural insights on TRPV5 gating by endogenous modulators.,Hughes TET, Pumroy RA, Yazici AT, Kasimova MA, Fluck EC, Huynh KW, Samanta A, Molugu SK, Zhou ZH, Carnevale V, Rohacs T, Moiseenkova-Bell VY Nat Commun. 2018 Oct 10;9(1):4198. doi: 10.1038/s41467-018-06753-6. PMID:30305626<ref>PMID:30305626</ref>
| + | ==See Also== |
| - | | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 6dmr" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: European rabbit]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hughes, T E.T]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Moiseenkova-Bell, V Y]] | + | [[Category: Hughes TET]] |
| - | [[Category: Pumroy, R A]] | + | [[Category: Moiseenkova-Bell VY]] |
| - | [[Category: Calcium channel]]
| + | [[Category: Pumroy RA]] |
| - | [[Category: Full-length]]
| + | |
| - | [[Category: Lipid-bound]] | + | |
| - | [[Category: Transport protein]]
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| - | [[Category: Trpv5]]
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