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| ==Inactivated state of 2-APB-bound wildtype rat TRPV2 in nanodiscs== | | ==Inactivated state of 2-APB-bound wildtype rat TRPV2 in nanodiscs== |
| <StructureSection load='7n0m' size='340' side='right'caption='[[7n0m]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='7n0m' size='340' side='right'caption='[[7n0m]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[7n0m]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N0M FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N0M FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FZ4:2-aminoethyl+diphenylborinate'>FZ4</scene></td></tr> | | </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=7n0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n0m OCA], [https://pdbe.org/7n0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n0m RCSB], [https://www.ebi.ac.uk/pdbsum/7n0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n0m 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=7n0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n0m OCA], [https://pdbe.org/7n0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n0m RCSB], [https://www.ebi.ac.uk/pdbsum/7n0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n0m ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function ==
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| [[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>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Transient receptor potential vanilloid 2 (TRPV2) is involved in many critical physiological and pathophysiological processes, making it a promising drug target. Here we present cryo-electron microscopy (cryo-EM) structures of rat TRPV2 in lipid nanodiscs activated by 2-aminoethoxydiphenyl borate (2-APB) and propose a TRPV2-specific 2-ABP binding site at the interface of S5 of one monomer and the S4-S5 linker of the adjacent monomer. In silico docking and electrophysiological studies confirm the key role of His521 and Arg539 in 2-APB activation of TRPV2. Additionally, electrophysiological experiments show that the combination of 2-APB and cannabidiol has a synergetic effect on TRPV2 activation, and cryo-EM structures demonstrate that both drugs were able to bind simultaneously. Together, our cryo-EM structures represent multiple functional states of the channel, providing a native picture of TRPV2 activation by small molecules and a structural framework for the development of TRPV2-specific activators.
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| Structural insights into TRPV2 activation by small molecules.,Pumroy RA, Protopopova AD, Fricke TC, Lange IU, Haug FM, Nguyen PT, Gallo PN, Sousa BB, Bernardes GJL, Yarov-Yarovoy V, Leffler A, Moiseenkova-Bell VY Nat Commun. 2022 Apr 28;13(1):2334. doi: 10.1038/s41467-022-30083-3. PMID:35484159<ref>PMID:35484159</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7n0m" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Gallo, P N]] | | [[Category: Gallo PN]] |
| [[Category: Moiseenkova-Bell, V Y]] | | [[Category: Moiseenkova-Bell VY]] |
| [[Category: Protopopova, A D]] | | [[Category: Protopopova AD]] |
| [[Category: Pumroy, R A]] | | [[Category: Pumroy RA]] |
| [[Category: Ion channel]]
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| [[Category: Transport protein]]
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| [[Category: Trp channel]]
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| [[Category: Trpv]]
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