|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the regulator of G-protein signaling domain of RGS6== | | ==Structure of the regulator of G-protein signaling domain of RGS6== |
| - | <StructureSection load='2es0' size='340' side='right' caption='[[2es0]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='2es0' size='340' side='right'caption='[[2es0]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2es0]] is a 1 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=2ES0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ES0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2es0]] is a 1 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=2ES0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ES0 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=2es0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2es0 OCA], [http://pdbe.org/2es0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2es0 RCSB], [http://www.ebi.ac.uk/pdbsum/2es0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2es0 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</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=2es0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2es0 OCA], [https://pdbe.org/2es0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2es0 RCSB], [https://www.ebi.ac.uk/pdbsum/2es0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2es0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RGS6_HUMAN RGS6_HUMAN]] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(o)-alpha is specifically enhanced by the RGS6/Gbeta5 dimer.<ref>PMID:10521509</ref> | + | [https://www.uniprot.org/uniprot/RGS6_HUMAN RGS6_HUMAN] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(o)-alpha is specifically enhanced by the RGS6/Gbeta5 dimer.<ref>PMID:10521509</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 27: |
Line 28: |
| | </div> | | </div> |
| | <div class="pdbe-citations 2es0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2es0" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Regulator of G-protein signaling 3D structures|Regulator of G-protein signaling 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Ball, L]] | + | [[Category: Arrowsmith C]] |
| - | [[Category: Delft, F von]] | + | [[Category: Ball L]] |
| - | [[Category: Doyle, D A]] | + | [[Category: Doyle DA]] |
| - | [[Category: Edwards, A]] | + | [[Category: Edwards A]] |
| - | [[Category: Elkins, J M]] | + | [[Category: Elkins JM]] |
| - | [[Category: Gilealdi, C]] | + | [[Category: Gilealdi C]] |
| - | [[Category: Johansson, C]] | + | [[Category: Johansson C]] |
| - | [[Category: Longman, E]] | + | [[Category: Longman E]] |
| - | [[Category: Niesen, F]] | + | [[Category: Niesen F]] |
| - | [[Category: Phillips, C]] | + | [[Category: Phillips C]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Schoch GA]] |
| - | [[Category: Schoch, G A]] | + | [[Category: Sobott F]] |
| - | [[Category: Sobott, F]] | + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Turnbull A]] |
| - | [[Category: Turnbull, A]] | + | [[Category: Von Delft F]] |
| - | [[Category: Domain swap]] | + | |
| - | [[Category: Human rgs6]]
| + | |
| - | [[Category: Regulator of g-protein signaling 6]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
RGS6_HUMAN Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(o)-alpha is specifically enhanced by the RGS6/Gbeta5 dimer.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Galpha subunits and thus facilitate termination of signaling initiated by G protein-coupled receptors (GPCRs). RGS proteins hold great promise as disease intervention points, given their signature role as negative regulators of GPCRs-receptors to which the largest fraction of approved medications are currently directed. RGS proteins share a hallmark RGS domain that interacts most avidly with Galpha when in its transition state for GTP hydrolysis; by binding and stabilizing switch regions I and II of Galpha, RGS domain binding consequently accelerates Galpha-mediated GTP hydrolysis. The human genome encodes more than three dozen RGS domain-containing proteins with varied Galpha substrate specificities. To facilitate their exploitation as drug-discovery targets, we have taken a systematic structural biology approach toward cataloging the structural diversity present among RGS domains and identifying molecular determinants of their differential Galpha selectivities. Here, we determined 14 structures derived from NMR and x-ray crystallography of members of the R4, R7, R12, and RZ subfamilies of RGS proteins, including 10 uncomplexed RGS domains and 4 RGS domain/Galpha complexes. Heterogeneity observed in the structural architecture of the RGS domain, as well as in engagement of switch III and the all-helical domain of the Galpha substrate, suggests that unique structural determinants specific to particular RGS protein/Galpha pairings exist and could be used to achieve selective inhibition by small molecules.
Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.,Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundstrom M, Doyle DA, Siderovski DP Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. Epub 2008 Apr 23. PMID:18434541[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Posner BA, Gilman AG, Harris BA. Regulators of G protein signaling 6 and 7. Purification of complexes with gbeta5 and assessment of their effects on g protein-mediated signaling pathways. J Biol Chem. 1999 Oct 22;274(43):31087-93. PMID:10521509
- ↑ Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundstrom M, Doyle DA, Siderovski DP. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. Epub 2008 Apr 23. PMID:18434541
|
