9pb5: Difference between revisions

Latest revision as of 06:51, 8 April 2026

Human TRPM8 menthol bound structure at 4 degrees Celsius resolved in cell vesicles using cryo-EM

Structural highlights

9pb5 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.5Å
Ligands:	XUQ
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2] ^[3] ^[4] ^[5] Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel.^[6] Negatively regulates menthol- and cold-induced channel activity by stabilizing the closed state of the channel.^[7]

References

↑ Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B. The principle of temperature-dependent gating in cold channels. Nature. 2004 Aug 12;430(7001):748-54. PMID:15306801 doi:10.1038/nature02732
↑ Rohács T, Lopes CM, Michailidis I, Logothetis DE. PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci. 2005 May;8(5):626-34. PMID:15852009 doi:10.1038/nn1451
↑ Thebault S, Lemonnier L, Bidaux G, Flourakis M, Bavencoffe A, Gordienko D, Roudbaraki M, Delcourt P, Panchin Y, Shuba Y, Skryma R, Prevarskaya N. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J Biol Chem. 2005 Nov 25;280(47):39423-35. PMID:16174775 doi:10.1074/jbc.M503544200
↑ Gkika D, Lemonnier L, Shapovalov G, Gordienko D, Poux C, Bernardini M, Bokhobza A, Bidaux G, Degerny C, Verreman K, Guarmit B, Benahmed M, de Launoit Y, Bindels RJ, Fiorio Pla A, Prevarskaya N. TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity. J Cell Biol. 2015 Jan 5;208(1):89-107. PMID:25559186 doi:10.1083/jcb.201402076
↑ Palchevskyi S, Czarnocki-Cieciura M, Vistoli G, Gervasoni S, Nowak E, Beccari AR, Nowotny M, Talarico C. Structure of human TRPM8 channel. Commun Biol. 2023 Oct 19;6(1):1065. PMID:37857704 doi:10.1038/s42003-023-05425-6
↑ Bidaux G, Beck B, Zholos A, Gordienko D, Lemonnier L, Flourakis M, Roudbaraki M, Borowiec AS, Fernández J, Delcourt P, Lepage G, Shuba Y, Skryma R, Prevarskaya N. Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms. J Biol Chem. 2012 Jan 27;287(5):2948-62. PMID:22128173 doi:10.1074/jbc.M111.270256
↑ Bidaux G, Beck B, Zholos A, Gordienko D, Lemonnier L, Flourakis M, Roudbaraki M, Borowiec AS, Fernández J, Delcourt P, Lepage G, Shuba Y, Skryma R, Prevarskaya N. Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms. J Biol Chem. 2012 Jan 27;287(5):2948-62. PMID:22128173 doi:10.1074/jbc.M111.270256

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OCA

[1] Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B. The principle of temperature-dependent gating in cold channels. Nature. 2004 Aug 12;430(7001):748-54. PMID:15306801 doi:10.1038/nature02732

[2] Rohács T, Lopes CM, Michailidis I, Logothetis DE. PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci. 2005 May;8(5):626-34. PMID:15852009 doi:10.1038/nn1451

[3] Thebault S, Lemonnier L, Bidaux G, Flourakis M, Bavencoffe A, Gordienko D, Roudbaraki M, Delcourt P, Panchin Y, Shuba Y, Skryma R, Prevarskaya N. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells. J Biol Chem. 2005 Nov 25;280(47):39423-35. PMID:16174775 doi:10.1074/jbc.M503544200

[4] Gkika D, Lemonnier L, Shapovalov G, Gordienko D, Poux C, Bernardini M, Bokhobza A, Bidaux G, Degerny C, Verreman K, Guarmit B, Benahmed M, de Launoit Y, Bindels RJ, Fiorio Pla A, Prevarskaya N. TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity. J Cell Biol. 2015 Jan 5;208(1):89-107. PMID:25559186 doi:10.1083/jcb.201402076

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

[6] Bidaux G, Beck B, Zholos A, Gordienko D, Lemonnier L, Flourakis M, Roudbaraki M, Borowiec AS, Fernández J, Delcourt P, Lepage G, Shuba Y, Skryma R, Prevarskaya N. Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms. J Biol Chem. 2012 Jan 27;287(5):2948-62. PMID:22128173 doi:10.1074/jbc.M111.270256

[7] Bidaux G, Beck B, Zholos A, Gordienko D, Lemonnier L, Flourakis M, Roudbaraki M, Borowiec AS, Fernández J, Delcourt P, Lepage G, Shuba Y, Skryma R, Prevarskaya N. Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms. J Biol Chem. 2012 Jan 27;287(5):2948-62. PMID:22128173 doi:10.1074/jbc.M111.270256

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@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[9pb5]] 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=9PB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PB5 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]] 3.5&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XUQ:(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexan-1-ol'>XUQ</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XUQ:(1~{R},2~{S},5~{R})-5-methyl-2-propan-2-yl-cyclohexan-1-ol'>XUQ</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=9pb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pb5 OCA], [https://pdbe.org/9pb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pb5 RCSB], [https://www.ebi.ac.uk/pdbsum/9pb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pb5 ProSAT]</span></td></tr>
 </table>

9pb5: Difference between revisions

Latest revision as of 06:51, 8 April 2026

Human TRPM8 menthol bound structure at 4 degrees Celsius resolved in cell vesicles using cryo-EM

Structural highlights

Function

References

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