7wre

From Proteopedia

(Difference between revisions)

Current revision

Mouse TRPM8 in lipid nanodiscs in the presence of calcium and icilin

Structural highlights

7wre is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.52Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A. A TRP channel that senses cold stimuli and menthol. Cell. 2002 Mar 8;108(5):705-15. doi: 10.1016/s0092-8674(02)00652-9. PMID:11893340 doi:http://dx.doi.org/10.1016/s0092-8674(02)00652-9
↑ Andersson DA, Chase HW, Bevan S. TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH. J Neurosci. 2004 Jun 9;24(23):5364-9. doi: 10.1523/JNEUROSCI.0890-04.2004. PMID:15190109 doi:http://dx.doi.org/10.1523/JNEUROSCI.0890-04.2004
↑ Zhao C, Xie Y, Xu L, Ye F, Xu X, Yang W, Yang F, Guo J. Structures of a mammalian TRPM8 in closed state. Nat Commun. 2022 Jun 3;13(1):3113. PMID:35662242 doi:10.1038/s41467-022-30919-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7wre"

Categories: Large Structures | Mus musculus | Guo J | Xie Y | Zhao C

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[7wre]] 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=7WRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WRE 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]] 2.52&#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)-3,4-dihydropyrimidin-2(1H)-one'>KX7</scene></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=7wre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wre OCA], [https://pdbe.org/7wre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wre RCSB], [https://www.ebi.ac.uk/pdbsum/7wre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wre ProSAT]</span></td></tr>
 </table>

7wre

From Proteopedia

Current revision

Mouse TRPM8 in lipid nanodiscs in the presence of calcium and icilin

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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