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| | ==Cryo-EM structure of rat TRPV6* in nanodiscs== | | ==Cryo-EM structure of rat TRPV6* in nanodiscs== |
| - | <StructureSection load='6bob' size='340' side='right' caption='[[6bob]], [[Resolution|resolution]] 3.90Å' scene=''> | + | <SX load='6bob' size='340' side='right' viewer='molstar' caption='[[6bob]], [[Resolution|resolution]] 3.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bob]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BOB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BOB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bob]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BOB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BOB FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpv6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=6bob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bob OCA], [http://pdbe.org/6bob PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bob RCSB], [http://www.ebi.ac.uk/pdbsum/6bob PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bob 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=6bob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bob OCA], [https://pdbe.org/6bob PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bob RCSB], [https://www.ebi.ac.uk/pdbsum/6bob PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bob ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRPV6_RAT TRPV6_RAT]] Calcium selective cation channel probably involved in Ca(2+) uptake in various tissues, including Ca(2+) reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:Q91WD2][UniProtKB:Q9H1D0]<ref>PMID:11287959</ref> | + | [https://www.uniprot.org/uniprot/TRPV6_RAT TRPV6_RAT] Calcium selective cation channel probably involved in Ca(2+) uptake in various tissues, including Ca(2+) reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:Q91WD2][UniProtKB:Q9H1D0]<ref>PMID:11287959</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6bob" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6bob" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Grassucci, R A]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: McGoldrick, L L]] | + | [[Category: Grassucci RA]] |
| - | [[Category: Saotome, K]] | + | [[Category: McGoldrick LL]] |
| - | [[Category: Singh, A K]] | + | [[Category: Saotome K]] |
| - | [[Category: Sobolevsky, A I]] | + | [[Category: Singh AK]] |
| - | [[Category: Twomey, E C]] | + | [[Category: Sobolevsky AI]] |
| - | [[Category: Yelshanskaya, M V]] | + | [[Category: Twomey EC]] |
| - | [[Category: Ion channel]]
| + | [[Category: Yelshanskaya MV]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
TRPV6_RAT Calcium selective cation channel probably involved in Ca(2+) uptake in various tissues, including Ca(2+) reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:Q91WD2][UniProtKB:Q9H1D0][1]
Publication Abstract from PubMed
Calcium-selective transient receptor potential vanilloid subfamily member 6 (TRPV6) channels play a critical role in calcium uptake in epithelial tissues. Altered TRPV6 expression is associated with a variety of human diseases, including cancers. TRPV6 channels are constitutively active and their open probability depends on the lipidic composition of the membrane in which they reside; it increases substantially in the presence of phosphatidylinositol 4,5-bisphosphate. Crystal structures of detergent-solubilized rat TRPV6 in the closed state have previously been solved. Corroborating electrophysiological results, these structures demonstrated that the Ca(2+) selectivity of TRPV6 arises from a ring of aspartate side chains in the selectivity filter that binds Ca(2+) tightly. However, how TRPV6 channels open and close their pores for ion permeation has remained unclear. Here we present cryo-electron microscopy structures of human TRPV6 in the open and closed states. The channel selectivity filter adopts similar conformations in both states, consistent with its explicit role in ion permeation. The iris-like channel opening is accompanied by an alpha-to-pi-helical transition in the pore-lining transmembrane helix S6 at an alanine hinge just below the selectivity filter. As a result of this transition, the S6 helices bend and rotate, exposing different residues to the ion channel pore in the open and closed states. This gating mechanism, which defines the constitutive activity of TRPV6, is, to our knowledge, unique among tetrameric ion channels and provides structural insights for understanding their diverse roles in physiology and disease.
Opening of the human epithelial calcium channel TRPV6.,McGoldrick LL, Singh AK, Saotome K, Yelshanskaya MV, Twomey EC, Grassucci RA, Sobolevsky AI Nature. 2017 Dec 20. pii: nature25182. doi: 10.1038/nature25182. PMID:29258289[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yue L, Peng JB, Hediger MA, Clapham DE. CaT1 manifests the pore properties of the calcium-release-activated calcium channel. Nature. 2001 Apr 5;410(6829):705-9. PMID:11287959 doi:http://dx.doi.org/10.1038/35070596
- ↑ McGoldrick LL, Singh AK, Saotome K, Yelshanskaya MV, Twomey EC, Grassucci RA, Sobolevsky AI. Opening of the human epithelial calcium channel TRPV6. Nature. 2017 Dec 20. pii: nature25182. doi: 10.1038/nature25182. PMID:29258289 doi:http://dx.doi.org/10.1038/nature25182
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