6kpf
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of a class A GPCR with G protein complex== | |
| + | <StructureSection load='6kpf' size='340' side='right'caption='[[6kpf]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6kpf]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KPF FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8D0:(6~{a}~{R},9~{R},10~{a}~{R})-9-(hydroxymethyl)-3-(8-isothiocyanato-2-methyl-octan-2-yl)-6,6-dimethyl-6~{a},7,8,9,10,10~{a}-hexahydrobenzo[c]chromen-1-ol'>8D0</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=6kpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kpf OCA], [http://pdbe.org/6kpf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kpf RCSB], [http://www.ebi.ac.uk/pdbsum/6kpf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kpf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[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/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> [[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/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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hindered the development of therapeutic applications. Importantly, missing structural information has significantly held back the development of promising CB2-selective agonist drugs for treating inflammatory and neuropathic pain without the psychoactivity of CB1. Here, we report the cryoelectron microscopy structures of synthetic cannabinoid-bound CB2 and CB1 in complex with Gi, as well as agonist-bound CB2 crystal structure. Of important scientific and therapeutic benefit, our results reveal a diverse activation and signaling mechanism, the structural basis of CB2-selective agonists design, and the unexpected interaction of cholesterol with CB1, suggestive of its endogenous allosteric modulating role. | ||
| - | + | Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex Structures.,Hua T, Li X, Wu L, Iliopoulos-Tsoutsouvas C, Wang Y, Wu M, Shen L, Johnston CA, Nikas SP, Song F, Song X, Yuan S, Sun Q, Wu Y, Jiang S, Grim TW, Benchama O, Stahl EL, Zvonok N, Zhao S, Bohn LM, Makriyannis A, Liu ZJ Cell. 2020 Jan 28. pii: S0092-8674(20)30055-6. doi: 10.1016/j.cell.2020.01.008. PMID:32004463<ref>PMID:32004463</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6kpf" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hua, T]] | ||
| + | [[Category: Li, X T]] | ||
| + | [[Category: Liu, Z J]] | ||
| + | [[Category: Makriyannis, A]] | ||
| + | [[Category: Shen, L]] | ||
| + | [[Category: Wang, Y X]] | ||
| + | [[Category: Wu, L J]] | ||
| + | [[Category: Gi protein]] | ||
| + | [[Category: Gpcr]] | ||
| + | [[Category: Membrane protein]] | ||
Revision as of 04:14, 13 February 2020
Cryo-EM structure of a class A GPCR with G protein complex
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Categories: Large Structures | Hua, T | Li, X T | Liu, Z J | Makriyannis, A | Shen, L | Wang, Y X | Wu, L J | Gi protein | Gpcr | Membrane protein
