8e4n
From Proteopedia
(Difference between revisions)
m (Protected "8e4n" [edit=sysop:move=sysop]) |
|||
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | The | + | ==The closed C1-state mouse TRPM8 structure in complex with PI(4,5)P2== |
| + | <StructureSection load='8e4n' size='340' side='right'caption='[[8e4n]], [[Resolution|resolution]] 3.07Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8e4n]] 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=8E4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E4N FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</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=8e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e4n OCA], [https://pdbe.org/8e4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e4n RCSB], [https://www.ebi.ac.uk/pdbsum/8e4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e4n 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Our knowledge of cold sensation and the therapeutic potential of TRPM8 for neuroinflammatory diseases and pain will be enhanced by understanding the structural basis of cooling agonist- and PIP2-dependent TRPM8 activation. We present cryo-electron microscopy structures of mouse TRPM8 in closed, intermediate, and open states along the ligand- and PIP2-dependent gating pathway. Our results uncover two discrete agonist sites, state-dependent rearrangements in the gate positions, and a disordered-to-ordered transition of the gate-forming S6-elucidating the molecular basis of chemically induced cool sensation in mammals. | ||
| - | + | Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP2.,Yin Y, Zhang F, Feng S, Butay KJ, Borgnia MJ, Im W, Lee SY Science. 2022 Oct 14;378(6616):eadd1268. doi: 10.1126/science.add1268. Epub 2022 , Oct 14. PMID:36227998<ref>PMID:36227998</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8e4n" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Borgnia MJ]] | ||
| + | [[Category: Butay KJ]] | ||
| + | [[Category: Feng S]] | ||
| + | [[Category: Im W]] | ||
| + | [[Category: Lee S-Y]] | ||
| + | [[Category: Yin Y]] | ||
| + | [[Category: Zhang F]] | ||
Current revision
The closed C1-state mouse TRPM8 structure in complex with PI(4,5)P2
| |||||||||||
Categories: Large Structures | Mus musculus | Borgnia MJ | Butay KJ | Feng S | Im W | Lee S-Y | Yin Y | Zhang F
