8t0e
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==TRPV1 in Nanodisc not bound with lysophosphatidic acid (apo)== | |
| + | <StructureSection load='8t0e' size='340' side='right'caption='[[8t0e]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8t0e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8T0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8T0E 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]] 3.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8IJ:[(2~{R})-2-octadecanoyloxy-3-[oxidanyl-[(2~{R},3~{R},5~{S},6~{R})-2,3,4,5,6-pentakis(oxidanyl)cyclohexyl]oxy-phosphoryl]oxy-propyl]+octadecanoate'>8IJ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=8t0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8t0e OCA], [https://pdbe.org/8t0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8t0e RCSB], [https://www.ebi.ac.uk/pdbsum/8t0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8t0e ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TRPV1_RAT TRPV1_RAT] Receptor-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. May be involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.<ref>PMID:9349813</ref> <ref>PMID:10644739</ref> <ref>PMID:11140687</ref> <ref>PMID:11418861</ref> <ref>PMID:12095983</ref> <ref>PMID:12194871</ref> <ref>PMID:12808128</ref> <ref>PMID:14523239</ref> <ref>PMID:12764195</ref> <ref>PMID:14630912</ref> <ref>PMID:15173182</ref> <ref>PMID:21076423</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for deciphering lipid modulation, which is relevant to understanding how pro-algesic agents enhance channel activity in the setting of inflammatory pain. Identification of a pocket within the TRPV1 transmembrane core has provided initial clues as to how phosphoinositide lipids bind to and regulate the channel. Here we show that this regulatory pocket in rat TRPV1 can accommodate diverse lipid species, including the inflammatory lipid lysophosphatidic acid, whose actions are determined by their specific modes of binding. Furthermore, we show that an empty-pocket channel lacking an endogenous phosphoinositide lipid assumes an agonist-like state, even at low temperature, substantiating the concept that phosphoinositide lipids serve as negative TRPV1 modulators whose ejection from the binding pocket is a critical step toward activation by thermal or chemical stimuli. | ||
| - | + | Structural basis of TRPV1 modulation by endogenous bioactive lipids.,Arnold WR, Mancino A, Moss FR 3rd, Frost A, Julius D, Cheng Y Nat Struct Mol Biol. 2024 Sep;31(9):1377-1385. doi: 10.1038/s41594-024-01299-2. , Epub 2024 May 2. PMID:38698206<ref>PMID:38698206</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8t0e" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Arnold WR]] | ||
| + | [[Category: Cheng Y]] | ||
Current revision
TRPV1 in Nanodisc not bound with lysophosphatidic acid (apo)
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