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| | <StructureSection load='6mhe' size='340' side='right'caption='[[6mhe]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='6mhe' size='340' side='right'caption='[[6mhe]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6mhe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MHE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MHE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6mhe]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MHE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gnai3, Gnai-3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=GOL:GLYCEROL'>GOL</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=6mhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mhe OCA], [http://pdbe.org/6mhe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mhe RCSB], [http://www.ebi.ac.uk/pdbsum/6mhe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mhe 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=6mhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mhe OCA], [https://pdbe.org/6mhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mhe RCSB], [https://www.ebi.ac.uk/pdbsum/6mhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mhe ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GNAI3_RAT GNAI3_RAT]] Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:2159473). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels. Stimulates the activity of receptor-regulated K(+) channels. The active GTP-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.[UniProtKB:P08754]<ref>PMID:2159473</ref> | + | [https://www.uniprot.org/uniprot/GNAI3_RAT GNAI3_RAT] Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:2159473). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels. Stimulates the activity of receptor-regulated K(+) channels. The active GTP-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.[UniProtKB:P08754]<ref>PMID:2159473</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 6mhe" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6mhe" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chang, G]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Ghosh, P]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Ilatovskiy, A]] | + | [[Category: Chang G]] |
| - | [[Category: Kalogriopoulos, N A]] | + | [[Category: Ghosh P]] |
| - | [[Category: Komives, E]] | + | [[Category: Ilatovskiy A]] |
| - | [[Category: Kopcho, N]] | + | [[Category: Kalogriopoulos NA]] |
| - | [[Category: Kufareva, I]] | + | [[Category: Komives E]] |
| - | [[Category: Ngo, T]] | + | [[Category: Kopcho N]] |
| - | [[Category: Rees, S D]] | + | [[Category: Kufareva I]] |
| - | [[Category: Sun, N]] | + | [[Category: Ngo T]] |
| - | [[Category: Exchange]]
| + | [[Category: Rees SD]] |
| - | [[Category: Gpcr]]
| + | [[Category: Sun N]] |
| - | [[Category: Inhibitory]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
GNAI3_RAT Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:2159473). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels. Stimulates the activity of receptor-regulated K(+) channels. The active GTP-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.[UniProtKB:P08754][1]
Publication Abstract from PubMed
Heterotrimeric G proteins are key molecular switches that control cell behavior. The canonical activation of G proteins by agonist-occupied G protein-coupled receptors (GPCRs) has recently been elucidated from the structural perspective. In contrast, the structural basis for GPCR-independent G protein activation by a novel family of guanine-nucleotide exchange modulators (GEMs) remains unknown. Here, we present a 2.0-A crystal structure of Galphai in complex with the GEM motif of GIV/Girdin. Nucleotide exchange assays, molecular dynamics simulations, and hydrogen-deuterium exchange experiments demonstrate that GEM binding to the conformational switch II causes structural changes that allosterically propagate to the hydrophobic core of the Galphai GTPase domain. Rearrangement of the hydrophobic core appears to be a common mechanism by which GPCRs and GEMs activate G proteins, although with different efficiency. Atomic-level insights presented here will aid structure-based efforts to selectively target the noncanonical G protein activation.
Structural basis for GPCR-independent activation of heterotrimeric Gi proteins.,Kalogriopoulos NA, Rees SD, Ngo T, Kopcho NJ, Ilatovskiy AV, Sun N, Komives EA, Chang G, Ghosh P, Kufareva I Proc Natl Acad Sci U S A. 2019 Jul 30. pii: 1906658116. doi:, 10.1073/pnas.1906658116. PMID:31363053[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Linder ME, Ewald DA, Miller RJ, Gilman AG. Purification and characterization of Go alpha and three types of Gi alpha after expression in Escherichia coli. J Biol Chem. 1990 May 15;265(14):8243-51. PMID:2159473
- ↑ Kalogriopoulos NA, Rees SD, Ngo T, Kopcho NJ, Ilatovskiy AV, Sun N, Komives EA, Chang G, Ghosh P, Kufareva I. Structural basis for GPCR-independent activation of heterotrimeric Gi proteins. Proc Natl Acad Sci U S A. 2019 Jul 30. pii: 1906658116. doi:, 10.1073/pnas.1906658116. PMID:31363053 doi:http://dx.doi.org/10.1073/pnas.1906658116
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