View source for 8bdc


==Human apo TRPM8 in a closed state (composite map)==
<StructureSection load='8bdc' size='340' side='right'caption='[[8bdc]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bdc]] 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=8BDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BDC 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]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=UND:UNDECANE'>UND</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8bdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bdc OCA], [https://pdbe.org/8bdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bdc RCSB], [https://www.ebi.ac.uk/pdbsum/8bdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bdc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRPM8_HUMAN TRPM8_HUMAN] Non-selective ion channel permeable to monovalent and divalent cations, including Na(+), K(+), and Ca(2+), with higher permeability for Ca(2+). Activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. Activated by cool temperatures (<23-28 degrees Celsius) and by chemical ligands evoking a sensation of coolness, such as menthol and icilin therefore plays a central role in the detection of environmental cold temperatures (PubMed:15306801, PubMed:15852009, PubMed:16174775, PubMed:25559186, PubMed:37857704). TRPM8 is a voltage-dependent channel; its activation by cold or chemical ligands shifts its voltage thresholds towards physiological membrane potentials, leading to the opening of the channel (PubMed:15306801). In addition to its critical role in temperature sensing, regulates basal tear secretion by sensing evaporation-induced cooling and changes in osmolality (By similarity). May plays a role in prostate cancer cell migration (PubMed:16174775, PubMed:25559186).[UniProtKB:Q8R4D5]<ref>PMID:15306801</ref> <ref>PMID:15852009</ref> <ref>PMID:16174775</ref> <ref>PMID:25559186</ref> <ref>PMID:37857704</ref>   Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel.<ref>PMID:22128173</ref>   Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel.<ref>PMID:22128173</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TRPM8 is a non-selective cation channel permeable to both monovalent and divalent cations that is activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. It is a therapeutic target for anticancer drug development, and its modulators can be utilized for several pathological conditions. Here, we present a cryo-electron microscopy structure of a human TRPM8 channel in the closed state that was solved at 2.7 A resolution. Our structure comprises the most complete model of the N-terminal pre-melastatin homology region. We also visualized several lipids that are bound by the protein and modeled how the human channel interacts with icilin. Analyses of pore helices in available TRPM structures showed that all these structures can be grouped into different closed, desensitized and open state conformations based on the register of the pore helix S6 which positions particular amino acid residues at the channel constriction.

Structure of human TRPM8 channel.,Palchevskyi S, Czarnocki-Cieciura M, Vistoli G, Gervasoni S, Nowak E, Beccari AR, Nowotny M, Talarico C Commun Biol. 2023 Oct 19;6(1):1065. doi: 10.1038/s42003-023-05425-6. PMID:37857704<ref>PMID:37857704</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bdc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Beccari AR]]
[[Category: Czarnocki-Cieciura M]]
[[Category: Gervasoni S]]
[[Category: Nowak E]]
[[Category: Nowotny M]]
[[Category: Palchevskyi S]]
[[Category: Talarico C]]
[[Category: Vistoli G]]