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| | <SX load='6d9h' size='340' side='right' viewer='molstar' caption='[[6d9h]], [[Resolution|resolution]] 3.60Å' scene=''> | | <SX load='6d9h' size='340' side='right' viewer='molstar' caption='[[6d9h]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d9h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D9H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D9H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d9h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D9H FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADN:ADENOSINE'>ADN</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]] 3.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GNAI2, GNAI2B ([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]), ADORA1 ([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=ADN:ADENOSINE'>ADN</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=6d9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d9h OCA], [http://pdbe.org/6d9h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d9h RCSB], [http://www.ebi.ac.uk/pdbsum/6d9h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d9h 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=6d9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d9h OCA], [https://pdbe.org/6d9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d9h RCSB], [https://www.ebi.ac.uk/pdbsum/6d9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d9h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACM4_HUMAN ACM4_HUMAN]] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase. [[http://www.uniprot.org/uniprot/GNAI2_HUMAN GNAI2_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. May play a role in cell division.<ref>PMID:17635935</ref> Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.<ref>PMID:17550964</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> | + | [https://www.uniprot.org/uniprot/GNAI2_HUMAN GNAI2_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. May play a role in cell division.<ref>PMID:17635935</ref> Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.<ref>PMID:17550964</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | + | *[[Muscarinic acetylcholine receptor|Muscarinic acetylcholine receptor]] |
| | *[[Transducin 3D structures|Transducin 3D structures]] | | *[[Transducin 3D structures|Transducin 3D structures]] |
| | == References == | | == References == |
| Line 26: |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baltos, J]] | + | [[Category: Baltos J]] |
| - | [[Category: Baumeister, W]] | + | [[Category: Baumeister W]] |
| - | [[Category: Christopoulos, A]] | + | [[Category: Christopoulos A]] |
| - | [[Category: Danev, R]] | + | [[Category: Danev R]] |
| - | [[Category: Draper-Joyce, C J]] | + | [[Category: Draper-Joyce CJ]] |
| - | [[Category: Furness, S G.B]] | + | [[Category: Furness SGB]] |
| - | [[Category: Glukhova, A]] | + | [[Category: Glukhova A]] |
| - | [[Category: Khoshouei, M]] | + | [[Category: Khoshouei M]] |
| - | [[Category: Liang, Y L]] | + | [[Category: Liang Y-L]] |
| - | [[Category: May, L T]] | + | [[Category: May LT]] |
| - | [[Category: Nguyen, A T.N]] | + | [[Category: Nguyen ATN]] |
| - | [[Category: Plitzko, J M]] | + | [[Category: Plitzko JM]] |
| - | [[Category: Sexton, P]] | + | [[Category: Sexton P]] |
| - | [[Category: Thal, D M]] | + | [[Category: Thal DM]] |
| - | [[Category: Venugopal, H]] | + | [[Category: Venugopal H]] |
| - | [[Category: Wootten, D]] | + | [[Category: Wootten D]] |
| - | [[Category: Active-state g protein-coupled receptor]]
| + | |
| - | [[Category: Adenosine a1 receptor]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
GNAI2_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. May play a role in cell division.[1] Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.[2]
Publication Abstract from PubMed
The class A adenosine A1 receptor (A1R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/o heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 A structure of the human A1R in complex with adenosine and heterotrimeric Gi2 protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive A1R, there is contraction at the extracellular surface in the orthosteric binding site mediated via movement of transmembrane domains 1 and 2. At the intracellular surface, the G protein engages the A1R primarily via amino acids in the C terminus of the Galphai alpha5-helix, concomitant with a 10.5 A outward movement of the A1R transmembrane domain 6. Comparison with the agonist-bound beta2 adrenergic receptor-Gs-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active A1R structure provides molecular insights into receptor and G-protein selectivity.
Structure of the adenosine-bound human adenosine A1 receptor-Gi complex.,Draper-Joyce CJ, Khoshouei M, Thal DM, Liang YL, Nguyen ATN, Furness SGB, Venugopal H, Baltos JA, Plitzko JM, Danev R, Baumeister W, May LT, Wootten D, Sexton PM, Glukhova A, Christopoulos A Nature. 2018 Jun;558(7711):559-563. doi: 10.1038/s41586-018-0236-6. Epub 2018 Jun, 20. PMID:29925945[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
- ↑ Lopez-Aranda MF, Acevedo MJ, Gutierrez A, Koulen P, Khan ZU. Role of a Galphai2 protein splice variant in the formation of an intracellular dopamine D2 receptor pool. J Cell Sci. 2007 Jul 1;120(Pt 13):2171-8. Epub 2007 Jun 5. PMID:17550964 doi:http://dx.doi.org/jcs.005611
- ↑ Draper-Joyce CJ, Khoshouei M, Thal DM, Liang YL, Nguyen ATN, Furness SGB, Venugopal H, Baltos JA, Plitzko JM, Danev R, Baumeister W, May LT, Wootten D, Sexton PM, Glukhova A, Christopoulos A. Structure of the adenosine-bound human adenosine A1 receptor-Gi complex. Nature. 2018 Jun;558(7711):559-563. doi: 10.1038/s41586-018-0236-6. Epub 2018 Jun, 20. PMID:29925945 doi:http://dx.doi.org/10.1038/s41586-018-0236-6
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