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| | <SX load='6nr4' size='340' side='right' viewer='molstar' caption='[[6nr4]], [[Resolution|resolution]] 4.30Å' scene=''> | | <SX load='6nr4' size='340' side='right' viewer='molstar' caption='[[6nr4]], [[Resolution|resolution]] 4.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nr4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Collared_flycatcher Collared flycatcher]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NR4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NR4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nr4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ficedula_albicollis Ficedula albicollis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NR4 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</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]] 4.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRPM8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=59894 Collared flycatcher])</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=6nr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nr4 OCA], [https://pdbe.org/6nr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nr4 RCSB], [https://www.ebi.ac.uk/pdbsum/6nr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nr4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6nr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nr4 OCA], [http://pdbe.org/6nr4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nr4 RCSB], [http://www.ebi.ac.uk/pdbsum/6nr4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nr4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Collared flycatcher]] | + | [[Category: Ficedula albicollis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Borgnia, M J]] | + | [[Category: Borgnia MJ]] |
| - | [[Category: Hsu, A L]] | + | [[Category: Hsu AL]] |
| - | [[Category: Le, S C]] | + | [[Category: Le SC]] |
| - | [[Category: Lee, S Y]] | + | [[Category: Lee S-Y]] |
| - | [[Category: Yang, H]] | + | [[Category: Yang H]] |
| - | [[Category: Yin, Y]] | + | [[Category: Yin Y]] |
| - | [[Category: Calcium-permeable channel]]
| + | |
| - | [[Category: Cold sensing]]
| + | |
| - | [[Category: Cooling agent]]
| + | |
| - | [[Category: Icilin]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Lipid sensing]]
| + | |
| - | [[Category: Menthol]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Trp channel]]
| + | |
| - | [[Category: Trpm channel]]
| + | |
| - | [[Category: Trpm8 channel]]
| + | |
| - | [[Category: Ws-12]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Transient receptor potential melastatin member 8 (TRPM8) is a Ca(2+)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling compounds relies on allosteric actions of agonist and membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2), but lack of structural information has thus far precluded a mechanistic understanding of ligand and lipid sensing by TRPM8. Using cryo-electron microscopy, we determined the structures of TRPM8 in complex with the synthetic cooling compound icilin, PIP2, and Ca(2+) and in complex with the menthol analog WS-12 and PIP2 Our structures reveal the binding sites for cooling agonists and PIP2 in TRPM8. Notably, PIP2 binds to TRPM8 in two different modes, which illustrate the mechanism of allosteric coupling between PIP2 and agonists. This study provides a platform for understanding the molecular mechanism of TRPM8 activation by cooling agents.
Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel.,Yin Y, Le SC, Hsu AL, Borgnia MJ, Yang H, Lee SY Science. 2019 Feb 7. pii: science.aav9334. doi: 10.1126/science.aav9334. PMID:30733385[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yin Y, Le SC, Hsu AL, Borgnia MJ, Yang H, Lee SY. Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel. Science. 2019 Feb 7. pii: science.aav9334. doi: 10.1126/science.aav9334. PMID:30733385 doi:http://dx.doi.org/10.1126/science.aav9334
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