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==CBD-bound full-length rat TRPV2 in nanodiscs, state 1==
==CBD-bound full-length rat TRPV2 in nanodiscs, state 1==
<StructureSection load='6u8a' size='340' side='right'caption='[[6u8a]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
<SX load='6u8a' size='340' side='right' viewer='molstar' caption='[[6u8a]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6u8a]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U8A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U8A FirstGlance]. <br>
<table><tr><td colspan='2'>[[6u8a]] 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=6U8A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U8A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P0T:cannabidiol'>P0T</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6u84|6u84]], [[6u85|6u85]], [[6u88|6u88]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6u8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8a OCA], [http://pdbe.org/6u8a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u8a RCSB], [http://www.ebi.ac.uk/pdbsum/6u8a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8a ProSAT]</span></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=6u8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8a OCA], [https://pdbe.org/6u8a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u8a RCSB], [https://www.ebi.ac.uk/pdbsum/6u8a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8a ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>
[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 ==
Transient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of Cannabis sativa, is an activator of TRPV2 and also modulates other transient receptor potential (TRP) channels. Here, we determined structures of the full-length rat TRPV2 channel in apo and CBD-bound states in nanodiscs by cryo-electron microscopy. We show that CBD interacts with TRPV2 through a hydrophobic pocket located between S5 and S6 helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. CBD-bound TRPV2 structures revealed that the S4-S5 linker plays a critical role in channel gating upon CBD binding. Additionally, nanodiscs permitted us to visualize two distinct TRPV2 apo states in a lipid environment. Together these results provide a foundation to further understand TRPV channel gating, their divergent physiological functions, and to accelerate structure-based drug design.


Molecular mechanism of TRPV2 channel modulation by cannabidiol.,Pumroy RA, Samanta A, Liu Y, Hughes TE, Zhao S, Yudin Y, Rohacs T, Han S, Moiseenkova-Bell VY Elife. 2019 Sep 30;8. pii: 48792. doi: 10.7554/eLife.48792. PMID:31566564<ref>PMID:31566564</ref>
==See Also==
 
*[[Ion channels 3D structures|Ion channels 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6u8a" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</SX>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Moiseenkova-Bell, V Y]]
[[Category: Rattus norvegicus]]
[[Category: Pumroy, R A]]
[[Category: Moiseenkova-Bell VY]]
[[Category: Cannabidiol]]
[[Category: Pumroy RA]]
[[Category: Ion channel]]
[[Category: Transport protein]]
[[Category: Trp channel]]
[[Category: Trpv2]]

Latest revision as of 09:28, 20 March 2024

CBD-bound full-length rat TRPV2 in nanodiscs, state 1

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