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| | ==Structure of the Regulator of G-Protein Signaling 17 (RGSZ2)== | | ==Structure of the Regulator of G-Protein Signaling 17 (RGSZ2)== |
| - | <StructureSection load='1zv4' size='340' side='right' caption='[[1zv4]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='1zv4' size='340' side='right'caption='[[1zv4]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zv4]] 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=1ZV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZV4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zv4]] 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=1ZV4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZV4 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RGS17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.4Å</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=1zv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zv4 OCA], [http://pdbe.org/1zv4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zv4 RCSB], [http://www.ebi.ac.uk/pdbsum/1zv4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zv4 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=1zv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zv4 OCA], [https://pdbe.org/1zv4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zv4 RCSB], [https://www.ebi.ac.uk/pdbsum/1zv4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zv4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RGS17_HUMAN RGS17_HUMAN]] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds selectively to G(z)-alpha and G(alpha)-i2 subunits, accelerates their GTPase activity and regulates their signaling activities. The G(z)-alpha activity is inhibited by the phosphorylation and palmitoylation of the G-protein. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity). | + | [https://www.uniprot.org/uniprot/RGS17_HUMAN RGS17_HUMAN] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds selectively to G(z)-alpha and G(alpha)-i2 subunits, accelerates their GTPase activity and regulates their signaling activities. The G(z)-alpha activity is inhibited by the phosphorylation and palmitoylation of the G-protein. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1zv4" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1zv4" 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: Bunkoczi, G]] | + | [[Category: Ball L]] |
| - | [[Category: Delft, F von]] | + | [[Category: Bunkoczi G]] |
| - | [[Category: Doyle, D A]] | + | [[Category: Doyle DA]] |
| - | [[Category: Edwards, A]] | + | [[Category: Edwards A]] |
| - | [[Category: Elkins, J M]] | + | [[Category: Elkins JM]] |
| - | [[Category: Gileadi, O]] | + | [[Category: Gileadi O]] |
| - | [[Category: Haroniti, A]] | + | [[Category: Haroniti A]] |
| - | [[Category: Jansson, A]] | + | [[Category: Jansson A]] |
| - | [[Category: Lee, W H]] | + | [[Category: Lee WH]] |
| - | [[Category: Marsden, B]] | + | [[Category: Marsden B]] |
| - | [[Category: Niesen, F H]] | + | [[Category: Niesen FH]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Schoch GA]] |
| - | [[Category: Schoch, G A]] | + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Turnbull AP]] |
| - | [[Category: Turnbull, A P]] | + | [[Category: Yang X]] |
| - | [[Category: Yang, X]] | + | [[Category: Von Delft F]] |
| - | [[Category: Human rgsz2]] | + | |
| - | [[Category: Mu-opioid receptor interacting protein]]
| + | |
| - | [[Category: Regulator of g-protein signaling]]
| + | |
| - | [[Category: Regulator of gz-selective protein signaling 2]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
RGS17_HUMAN Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds selectively to G(z)-alpha and G(alpha)-i2 subunits, accelerates their GTPase activity and regulates their signaling activities. The G(z)-alpha activity is inhibited by the phosphorylation and palmitoylation of the G-protein. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
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