8bdc
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Human apo TRPM8 in a closed state (composite map)== | |
| + | <StructureSection load='8bdc' size='340' side='right'caption='[[8bdc]], [[Resolution|resolution]] 2.65Å' 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]] 2.65Å</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] 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 agonist 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. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration (PubMed:25559186). Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.<ref>PMID:15306801</ref> <ref>PMID:16174775</ref> <ref>PMID:22128173</ref> <ref>PMID:25559186</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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </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]] | ||
Revision as of 13:02, 1 November 2023
Human apo TRPM8 in a closed state (composite map)
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