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| | <StructureSection load='3qe0' size='340' side='right'caption='[[3qe0]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='3qe0' size='340' side='right'caption='[[3qe0]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qe0]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QE0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qe0]] is a 5 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=3QE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QE0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qi2|3qi2]], [[2om2|2om2]], [[1kjy|1kjy]], [[1y3a|1y3a]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GNAI1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Heterotrimeric_G-protein_GTPase Heterotrimeric G-protein GTPase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.1 3.6.5.1] </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=3qe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qe0 OCA], [https://pdbe.org/3qe0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qe0 RCSB], [https://www.ebi.ac.uk/pdbsum/3qe0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qe0 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=3qe0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qe0 OCA], [https://pdbe.org/3qe0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qe0 RCSB], [https://www.ebi.ac.uk/pdbsum/3qe0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qe0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_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. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref>
| + | [https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_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. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Heterotrimeric G-proteins are molecular switches integral to a panoply of different physiological responses that many organisms make to environmental cues. The switch from inactive to active Galphabetagamma heterotrimer relies on nucleotide cycling by the Galpha subunit: exchange of GTP for GDP activates Galpha, whereas its intrinsic enzymatic activity catalyzes GTP hydrolysis to GDP and inorganic phosphate, thereby reverting Galpha to its inactive state. In several genetic studies of filamentous fungi, such as the rice blast fungus Magnaporthe oryzae, a G42R mutation in the phosphate-binding loop of Galpha subunits is assumed to be GTPase-deficient and thus constitutively active. Here, we demonstrate that Galpha(G42R) mutants are not GTPase deficient, but rather incapable of achieving the activated conformation. Two crystal structure models suggest that Arg-42 prevents a typical switch region conformational change upon Galpha(i1)(G42R) binding to GDP.AlF(4) (-) or GTP, but rotameric flexibility at this locus allows for unperturbed GTP hydrolysis. Galpha(G42R) mutants do not engage the active state-selective peptide KB-1753 nor RGS domains with high affinity, but instead favor interaction with Gbetagamma and GoLoco motifs in any nucleotide state. The corresponding Galpha(q)(G48R) mutant is not constitutively active in cells and responds poorly to aluminum tetrafluoride activation. Comparative analyses of M. oryzae strains harboring either G42R or GTPase-deficient Q/L mutations in the Galpha subunits MagA or MagB illustrate functional differences in environmental cue processing and intracellular signaling outcomes between these two Galpha mutants, thus demonstrating the in vivo functional divergence of G42R and activating G-protein mutants.
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| - | | + | |
| - | A P-loop Mutation in Galpha Subunits Prevents Transition to the Active State: Implications for G-protein Signaling in Fungal Pathogenesis.,Bosch DE, Willard FS, Ramanujam R, Kimple AJ, Willard MD, Naqvi NI, Siderovski DP PLoS Pathog. 2012 Feb;8(2):e1002553. Epub 2012 Feb 23. PMID:22383884<ref>PMID:22383884</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3qe0" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Heterotrimeric G-protein GTPase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bosch, D E]] | + | [[Category: Bosch DE]] |
| - | [[Category: Kimple, A J]] | + | [[Category: Kimple AJ]] |
| - | [[Category: Miley, M J]] | + | [[Category: Miley MJ]] |
| - | [[Category: Siderovski, D P]] | + | [[Category: Siderovski DP]] |
| - | [[Category: Willard, F S]] | + | [[Category: Willard FS]] |
| - | [[Category: Adp-ribosylation]]
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| - | [[Category: All-helical domain]]
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| - | [[Category: Arginine finger]]
| + | |
| - | [[Category: Gtp binding]]
| + | |
| - | [[Category: Gtpase activity]]
| + | |
| - | [[Category: Kb752]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Nucleotide binding]]
| + | |
| - | [[Category: Ras-like domain]]
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| - | [[Category: Signaling protein]]
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| - | [[Category: Transducer]]
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