View source for 8slx


==Rat TRPV2 bound with 1 CBD ligand in nanodiscs==
<StructureSection load='8slx' size='340' side='right'caption='[[8slx]], [[Resolution|resolution]] 3.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8slx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=8fx8 8fx8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SLX 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]] 3.23&#8491;</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=P0T:cannabidiol'>P0T</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=8slx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8slx OCA], [https://pdbe.org/8slx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8slx RCSB], [https://www.ebi.ac.uk/pdbsum/8slx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8slx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRPV2_RAT TRPV2_RAT] Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by growth factors, like IGF1, PDGF and morphogenetic neuropeptide/head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH (By similarity).<ref>PMID:10201375</ref> <ref>PMID:15249591</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cation-permeable TRPV2 channel is important for cardiac and immune cell function. Cannabidiol (CBD), a non-psychoactive cannabinoid of clinical relevance, is one of the few molecules known to activate TRPV2. Using the patch-clamp technique, we discover that CBD can sensitize current responses of the rat TRPV2 channel to the synthetic agonist 2-aminoethoxydiphenyl borate (2-APB) by over two orders of magnitude, without sensitizing channels to activation by moderate (40 degrees C) heat. Using cryo-EM, we uncover a new small-molecule binding site in the pore domain of rTRPV2 in addition to a nearby CBD site that had already been reported. The TRPV1 and TRPV3 channels are also activated by 2-APB and CBD and share multiple conserved features with TRPV2, but we find that strong sensitization by CBD is only observed in TRPV3, while sensitization for TRPV1 is much weaker. Mutations at non-conserved positions between rTRPV2 and rTRPV1 in either the pore domain or the CBD sites failed to confer strong sensitization by CBD in mutant rTRPV1 channels. Together, our results indicate that CBD-dependent sensitization of rTRPV2 channels engages multiple channel regions, and that the difference in sensitization strength between rTRPV2 and rTRPV1 channels does not originate from amino acid sequence differences at the CBD binding site or the pore domain. The remarkably robust effect of CBD on TRPV2 and TRPV3 channels offers a promising new tool to both understand and overcome one of the major roadblocks in the study of these channels - their resilience to activation.

Cannabidiol sensitizes TRPV2 channels to activation by 2-APB.,Gochman A, Tan XF, Bae C, Chen H, Swartz KJ, Jara-Oseguera A Elife. 2023 May 18;12:e86166. doi: 10.7554/eLife.86166. PMID:37199723<ref>PMID:37199723</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8slx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Swartz KJ]]
[[Category: Tan X]]