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6u88

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Revision as of 09:47, 8 January 2020

CBD-bound full-length rat TRPV2 in nanodiscs, state 2

Structural highlights

6u88 is a 4 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Trpv2, Sac2b, Vrl1 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature. 1999 Apr 1;398(6726):436-41. PMID:10201375 doi:http://dx.doi.org/10.1038/18906
↑ Stokes AJ, Shimoda LM, Koblan-Huberson M, Adra CN, Turner H. A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells. J Exp Med. 2004 Jul 19;200(2):137-47. Epub 2004 Jul 12. PMID:15249591 doi:http://dx.doi.org/10.1084/jem.20032082
↑ Pumroy RA, Samanta A, Liu Y, Hughes TE, Zhao S, Yudin Y, Rohacs T, Han S, Moiseenkova-Bell VY. Molecular mechanism of TRPV2 channel modulation by cannabidiol. Elife. 2019 Sep 30;8. pii: 48792. doi: 10.7554/eLife.48792. PMID:31566564 doi:http://dx.doi.org/10.7554/eLife.48792

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6u88"

@@ Line 3: / Line 3: @@
 <StructureSection load='6u88' size='340' side='right'caption='[[6u88]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6u88]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U88 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U88 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6u88]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U88 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U88 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>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Trpv2, Sac2b, Vrl1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=6u88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u88 OCA], [http://pdbe.org/6u88 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u88 RCSB], [http://www.ebi.ac.uk/pdbsum/6u88 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u88 ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
 [[Category: Large Structures]]
 [[Category: Moiseenkova-Bell, V Y]]

6u88

From Proteopedia

Revision as of 09:47, 8 January 2020

CBD-bound full-length rat TRPV2 in nanodiscs, state 2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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