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| | ==Solution Structure of a peptide mimetic of the fourth cytoplasmic loop of the G-protein coupled CB1 cannabinoid receptor== | | ==Solution Structure of a peptide mimetic of the fourth cytoplasmic loop of the G-protein coupled CB1 cannabinoid receptor== |
| - | <StructureSection load='2b0y' size='340' side='right'caption='[[2b0y]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2b0y' size='340' side='right'caption='[[2b0y]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2b0y]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B0Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2B0Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2b0y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B0Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B0Y FirstGlance]. <br> |
| - | </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=2b0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b0y OCA], [http://pdbe.org/2b0y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2b0y RCSB], [http://www.ebi.ac.uk/pdbsum/2b0y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2b0y ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2b0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b0y OCA], [https://pdbe.org/2b0y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b0y RCSB], [https://www.ebi.ac.uk/pdbsum/2b0y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b0y ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CNR1_HUMAN CNR1_HUMAN]] Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.<ref>PMID:15620723</ref> | + | [https://www.uniprot.org/uniprot/CNR1_HUMAN CNR1_HUMAN] Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.<ref>PMID:15620723</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cowsik, S M]] | + | [[Category: Cowsik SM]] |
| - | [[Category: Grace, C R]] | + | [[Category: Grace CR]] |
| - | [[Category: Howlett, A C]] | + | [[Category: Howlett AC]] |
| - | [[Category: Shim, J Y]] | + | [[Category: Shim JY]] |
| - | [[Category: Welsh, W J]] | + | [[Category: Welsh WJ]] |
| - | [[Category: Cb1 cannabinoid receptor]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cell surface receptor]]
| + | |
| - | [[Category: Dqf-cosy]]
| + | |
| - | [[Category: G-protein coupled receptor]]
| + | |
| - | [[Category: Gtp-binding protein]]
| + | |
| - | [[Category: Noesy]]
| + | |
| - | [[Category: Roesy]]
| + | |
| - | [[Category: Signal transduction mechanism]]
| + | |
| - | [[Category: Tocsy]]
| + | |
| Structural highlights
Function
CNR1_HUMAN Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.[1]
Publication Abstract from PubMed
The proximal portion of the C-terminus of the CB(1) cannabinoid receptor is a primary determinant for G-protein activation. A 17 residue proximal C-terminal peptide (rodent CB1 401-417), the intracellular loop 4 (IL4) peptide, mimicked the receptor's G-protein activation domain. Because of the importance of the cationic amino acids to G-protein activation, the three-dimensional structure of the IL4 peptide in a negatively charged sodium dodecyl sulfate (SDS) micellar environment has been studied by two-dimensional proton nuclear magnetic resonance (2D (1)H NMR) spectroscopy and distance geometry calculations. Unambiguous proton NMR assignments were carried out with the aid of correlation spectroscopy (DQF-COSY and TOCSY) and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The distance constraints were used in torsion angle dynamics algorithm for NMR applications (DYANA) to generate a family of structures which were refined using restrained energy minimization and dynamics. In water, the IL4 peptide prefers an extended conformation, whereas in SDS micelles, 3(10)-helical conformation is induced. The predominance of 3(10)-helical domain structure in SDS represents a unique difference compared with structure in alternative environments, which can significantly impact global electrostatic surface potential on the cytoplasmic surface of the CB(1) receptor and might influence the signal to the G-proteins.
Unique helical conformation of the fourth cytoplasmic loop of the CB1 cannabinoid receptor in a negatively charged environment.,Grace CR, Cowsik SM, Shim JY, Welsh WJ, Howlett AC J Struct Biol. 2007 Sep;159(3):359-68. Epub 2007 Apr 20. PMID:17524664[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ryberg E, Vu HK, Larsson N, Groblewski T, Hjorth S, Elebring T, Sjogren S, Greasley PJ. Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett. 2005 Jan 3;579(1):259-64. PMID:15620723 doi:http://dx.doi.org/10.1016/j.febslet.2004.11.085
- ↑ Grace CR, Cowsik SM, Shim JY, Welsh WJ, Howlett AC. Unique helical conformation of the fourth cytoplasmic loop of the CB1 cannabinoid receptor in a negatively charged environment. J Struct Biol. 2007 Sep;159(3):359-68. Epub 2007 Apr 20. PMID:17524664 doi:10.1016/j.jsb.2007.04.004
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