View source for 7wrc


==Mouse TRPM8 in LMNG in the presence of calcium, icilin and PI(4,5)P2==
<StructureSection load='7wrc' size='340' side='right'caption='[[7wrc]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wrc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WRC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WRC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.21&#8491;</td></tr>
<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=KX7:3-(2-hydroxyphenyl)-6-(3-nitrophenyl)-1,4-dihydropyrimidin-2-one'>KX7</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=7wrc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wrc OCA], [https://pdbe.org/7wrc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wrc RCSB], [https://www.ebi.ac.uk/pdbsum/7wrc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wrc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRPM8_MOUSE TRPM8_MOUSE] Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonists menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing.<ref>PMID:11893340</ref> <ref>PMID:15190109</ref> 
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== Publication Abstract from PubMed ==
Transient receptor potential melastatin 8 (TRPM8) channel is a Ca(2+)-permeable non-selective cation channel that acts as the primary cold sensor in humans. TRPM8 is also activated by ligands such as menthol, icilin, and phosphatidylinositol 4,5-bisphosphate (PIP(2)), and desensitized by Ca(2+). Here we have determined electron cryo-microscopy structures of mouse TRPM8 in the absence of ligand, and in the presence of Ca(2+) and icilin at 2.5-3.2 A resolution. The ligand-free state TRPM8 structure represents the full-length structure of mammalian TRPM8 channels with a canonical S4-S5 linker and the clearly resolved selectivity filter and outer pore loop. TRPM8 has a short but wide selectivity filter which may account for its permeability to hydrated Ca(2+). Ca(2+) and icilin bind in the cytosolic-facing cavity of the voltage-sensing-like domain of TRPM8 but induce little conformational change. All the ligand-bound TRPM8 structures adopt the same closed conformation as the ligand-free structure. This study reveals the overall architecture of mouse TRPM8 and the structural basis for its ligand recognition.

Structures of a mammalian TRPM8 in closed state.,Zhao C, Xie Y, Xu L, Ye F, Xu X, Yang W, Yang F, Guo J Nat Commun. 2022 Jun 3;13(1):3113. doi: 10.1038/s41467-022-30919-y. PMID:35662242<ref>PMID:35662242</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wrc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Guo J]]
[[Category: Xie Y]]
[[Category: Zhao C]]