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| | ==Structure of regulator of G protein signaling 8 (RGS8) in complex with AlF4-activated Galpha-q== | | ==Structure of regulator of G protein signaling 8 (RGS8) in complex with AlF4-activated Galpha-q== |
| - | <StructureSection load='5do9' size='340' side='right' caption='[[5do9]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='5do9' size='340' side='right'caption='[[5do9]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5do9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DO9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DO9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5do9]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DO9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gnaq ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), RGS8 ([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=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5do9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5do9 OCA], [http://pdbe.org/5do9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5do9 RCSB], [http://www.ebi.ac.uk/pdbsum/5do9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5do9 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=5do9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5do9 OCA], [https://pdbe.org/5do9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5do9 RCSB], [https://www.ebi.ac.uk/pdbsum/5do9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5do9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GNAQ_MOUSE GNAQ_MOUSE]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro).<ref>PMID:17938235</ref> <ref>PMID:20624888</ref> [[http://www.uniprot.org/uniprot/RGS8_HUMAN RGS8_HUMAN]] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Preferentially binds to G(o)-alpha and G(i)-alpha-3 (By similarity). | + | [https://www.uniprot.org/uniprot/GNAQ_MOUSE GNAQ_MOUSE] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro).<ref>PMID:17938235</ref> <ref>PMID:20624888</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5do9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5do9" 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: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Taylor, V G]] | + | [[Category: Mus musculus]] |
| - | [[Category: Tesmer, J J.G]] | + | [[Category: Taylor VG]] |
| - | [[Category: Gq-g11]] | + | [[Category: Tesmer JJG]] |
| - | [[Category: Gtp-binding protein alpha subunit]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Rgs protein]]
| + | |
| Structural highlights
Function
GNAQ_MOUSE Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro).[1] [2]
Publication Abstract from PubMed
Regulator of G protein signaling (RGS) proteins interact with activated Galpha subunits via their RGS domains and accelerate the hydrolysis of GTP. Whereas the R4 subfamily of RGS proteins generally accepts both Galphai/o and Galphaq/11 subunits as substrates, the R7 and R12 subfamilies select against Galphaq/11. In contrast, only one RGS protein, RGS2, is known to be selective for Galphaq/11. The molecular basis for this selectivity is not clear. Previously, the crystal structure of RGS2 in complex with Galphaq revealed a non-canonical interaction that could be due to interfacial differences imposed by RGS2, the Galpha subunit, or both. To resolve this ambiguity, the 2.6 A crystal structure of RGS8, an R4 subfamily member, was determined in complex with Galphaq. RGS8 adopts the same pose on Galphaq as it does when bound to Galphai3, indicating that the non-canonical interaction of RGS2 with Galphaq is due to unique features of RGS2. Based on the RGS8 structure, residues in RGS8 that contact a unique alpha-helical domain loop of Galphaq were converted to those typically found in R12 subfamily members, and the reverse substitutions were introduced into RGS10, an R12 subfamily member. Although these substitutions perturbed their ability to stimulate GTP hydrolysis, they did not reverse selectivity. Instead, selectivity for Galphaq seems more likely determined by whether strong contacts can be maintained between alpha of the RGS domain and Switch III of Galphaq, regions of high sequence and conformational diversity in both protein families.
Structure of the Regulator of G Protein Signaling 8 (RGS8)-Galphaq Complex: Molecular Basis for Galpha Selectivity.,Taylor VG, Bommarito PA, Tesmer JJ J Biol Chem. 2016 Jan 11. pii: jbc.M115.712075. PMID:26755720[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shi G, Partida-Sanchez S, Misra RS, Tighe M, Borchers MT, Lee JJ, Simon MI, Lund FE. Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. J Exp Med. 2007 Oct 29;204(11):2705-18. Epub 2007 Oct 15. PMID:17938235 doi:10.1084/jem.20071267
- ↑ Misra RS, Shi G, Moreno-Garcia ME, Thankappan A, Tighe M, Mousseau B, Kusser K, Becker-Herman S, Hudkins KL, Dunn R, Kehry MR, Migone TS, Marshak-Rothstein A, Simon M, Randall TD, Alpers CE, Liggitt D, Rawlings DJ, Lund FE. G alpha q-containing G proteins regulate B cell selection and survival and are required to prevent B cell-dependent autoimmunity. J Exp Med. 2010 Aug 2;207(8):1775-89. doi: 10.1084/jem.20092735. Epub 2010 Jul, 12. PMID:20624888 doi:10.1084/jem.20092735
- ↑ Taylor VG, Bommarito PA, Tesmer JJ. Structure of the Regulator of G Protein Signaling 8 (RGS8)-Galphaq Complex: Molecular Basis for Galpha Selectivity. J Biol Chem. 2016 Jan 11. pii: jbc.M115.712075. PMID:26755720 doi:http://dx.doi.org/10.1074/jbc.M115.712075
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