6am3: Difference between revisions
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==Regulator of G protein signaling (RGS) 17 in complex with Ca2+== | ==Regulator of G protein signaling (RGS) 17 in complex with Ca2+== | ||
<StructureSection load='6am3' size='340' side='right' caption='[[6am3]], [[Resolution|resolution]] 1.53Å' scene=''> | <StructureSection load='6am3' size='340' side='right'caption='[[6am3]], [[Resolution|resolution]] 1.53Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6am3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AM3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AM3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6am3]] is a 2 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=6AM3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AM3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RGS17, RGSZ2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6am3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6am3 OCA], [http://pdbe.org/6am3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6am3 RCSB], [http://www.ebi.ac.uk/pdbsum/6am3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6am3 ProSAT]</span></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=6am3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6am3 OCA], [http://pdbe.org/6am3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6am3 RCSB], [http://www.ebi.ac.uk/pdbsum/6am3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6am3 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). | [[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). | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Regulator of G protein signaling (RGS) proteins are negative regulators of G protein-coupled receptor (GPCR) signaling through their ability to act as GTPase-activating proteins (GAPs) for activated Galpha subunits. Members of the RZ subfamily of RGS proteins bind to activated Galphao, Galphaz, and Galphai1-3 proteins in the nervous system and thereby inhibit downstream pathways, including those involved in Ca(2+)-dependent signaling. In contrast to other RGS proteins, little is known about RZ subfamily structure and regulation. Herein, we present the 1.5-A crystal structure of RGS17, the most complete and highest-resolution structure of an RZ subfamily member to date. RGS17 cocrystallized with Ca(2+) bound to conserved positions on the predicted Galpha-binding surface of the protein. Using NMR chemical shift perturbations, we confirmed that Ca(2+) binds in solution to the same site. Furthermore, RGS17 had greater than 55-fold higher affinity for Ca(2+) than for Mg(2+) Finally, we found that Ca(2+) promotes interactions between RGS17 and activated Galpha and decreases the Km for GTP hydrolysis, potentially by altering the binding mechanism between these proteins. Taken together, these findings suggest that Ca(2+) positively regulates RGS17, which may represent a general mechanism by which increased Ca(2+) concentration promotes the GAP activity of the RZ subfamily, leading to RZ-mediated inhibition of Ca(2+) signaling. | |||
High-resolution structure of RGS17 suggests a role for Ca(2+) in promoting the GTPase-activating protein activity by RZ subfamily members.,Sieng M, Hayes MP, O'Brien JB, Andrew Fowler C, Houtman JC, Roman DL, Lyon AM J Biol Chem. 2019 May 17;294(20):8148-8160. doi: 10.1074/jbc.RA118.006059. Epub, 2019 Apr 2. PMID:30940727<ref>PMID:30940727</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6am3" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Lyon, A M]] | [[Category: Lyon, A M]] | ||
[[Category: Sieng, M]] | [[Category: Sieng, M]] |