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| | <SX load='6pt0' size='340' side='right' viewer='molstar' caption='[[6pt0]], [[Resolution|resolution]] 3.20Å' scene=''> | | <SX load='6pt0' size='340' side='right' viewer='molstar' caption='[[6pt0]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pt0]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PT0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PT0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pt0]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PT0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=WI5:{(3R)-5-methyl-3-[(morpholin-4-yl)methyl]-2,3-dihydro[1,4]oxazino[2,3,4-hi]indol-6-yl}(naphthalen-1-yl)methanone'>WI5</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]] 3.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNR2, CB2A, CB2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNAI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=WI5:[(11~{R})-2-methyl-11-(morpholin-4-ylmethyl)-9-oxa-1-azatricyclo[6.3.1.0^{4,12}]dodeca-2,4(12),5,7-tetraen-3-yl]-naphthalen-1-yl-methanone'>WI5</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pt0 OCA], [http://pdbe.org/6pt0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pt0 RCSB], [http://www.ebi.ac.uk/pdbsum/6pt0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pt0 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=6pt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pt0 OCA], [https://pdbe.org/6pt0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pt0 RCSB], [https://www.ebi.ac.uk/pdbsum/6pt0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pt0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity). [[http://www.uniprot.org/uniprot/CNR2_HUMAN CNR2_HUMAN]] Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.<ref>PMID:10051546</ref> <ref>PMID:12663043</ref> <ref>PMID:12711605</ref> <ref>PMID:18692962</ref> [[http://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> [[http://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref> | + | [https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</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__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Chen, M]] | + | [[Category: Chen M]] |
| - | [[Category: Feng, Z]] | + | [[Category: Feng Z]] |
| - | [[Category: Liu, H]] | + | [[Category: Liu H]] |
| - | [[Category: McGuire, T]] | + | [[Category: McGuire T]] |
| - | [[Category: Melcher, K]] | + | [[Category: Melcher K]] |
| - | [[Category: Meng, X]] | + | [[Category: Meng X]] |
| - | [[Category: Wang, J]] | + | [[Category: Wang J]] |
| - | [[Category: Wang, L]] | + | [[Category: Wang L]] |
| - | [[Category: Xie, X Q]] | + | [[Category: Xie XQ]] |
| - | [[Category: Xing, C]] | + | [[Category: Xing C]] |
| - | [[Category: Xu, H E]] | + | [[Category: Xu HE]] |
| - | [[Category: Xu, T H]] | + | [[Category: Xu TH]] |
| - | [[Category: Xue, Y]] | + | [[Category: Xue Y]] |
| - | [[Category: Zhang, C]] | + | [[Category: Zhang C]] |
| - | [[Category: Zhao, G]] | + | [[Category: Zhao G]] |
| - | [[Category: Zhou, X E]] | + | [[Category: Zhou XE]] |
| - | [[Category: Zhuang, Y]] | + | [[Category: Zhuang Y]] |
| - | [[Category: 212-2]]
| + | |
| - | [[Category: Gpcr complex]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Win55]]
| + | |
| Structural highlights
Function
GNAI1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.[1] [2]
Publication Abstract from PubMed
Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the human CB2-Gi signaling complex bound to the agonist WIN 55,212-2. The 3D structure reveals the binding mode of WIN 55,212-2 and structural determinants for distinguishing CB2 agonists from antagonists, which are supported by a pair of rationally designed agonist and antagonist. Further structural analyses with computational docking results uncover the differences between CB2 and CB1 in receptor activation, ligand recognition, and Gi coupling. These findings are expected to facilitate rational structure-based discovery of drugs targeting the cannabinoid system.
Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex.,Xing C, Zhuang Y, Xu TH, Feng Z, Zhou XE, Chen M, Wang L, Meng X, Xue Y, Wang J, Liu H, McGuire TF, Zhao G, Melcher K, Zhang C, Xu HE, Xie XQ Cell. 2020 Jan 28. pii: S0092-8674(20)30054-4. doi: 10.1016/j.cell.2020.01.007. PMID:32004460[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
- ↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
- ↑ Xing C, Zhuang Y, Xu TH, Feng Z, Zhou XE, Chen M, Wang L, Meng X, Xue Y, Wang J, Liu H, McGuire TF, Zhao G, Melcher K, Zhang C, Xu HE, Xie XQ. Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. Cell. 2020 Jan 28. pii: S0092-8674(20)30054-4. doi: 10.1016/j.cell.2020.01.007. PMID:32004460 doi:http://dx.doi.org/10.1016/j.cell.2020.01.007
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