2v4z

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{{STRUCTURE_2v4z| PDB=2v4z | SCENE= }}
 
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===THE CRYSTAL STRUCTURE OF THE HUMAN G-PROTEIN SUBUNIT ALPHA (GNAI3) IN COMPLEX WITH AN ENGINEERED REGULATOR OF G-PROTEIN SIGNALING TYPE 2 DOMAIN (RGS2)===
 
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{{ABSTRACT_PUBMED_19478087}}
 
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==Function==
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==The crystal structure of the human G-protein subunit alpha (GNAI3) in complex with an engineered regulator of G-protein signaling type 2 domain (RGS2)==
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[[http://www.uniprot.org/uniprot/RGS2_HUMAN RGS2_HUMAN]] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. May play a role in leukemogenesis. Plays a role in negative feedback control pathway for adenylyl cyclase signaling. Binds EIF2B5 and blocks its activity, thereby inhibiting the translation of mRNA into protein.<ref>PMID:11278586</ref><ref>PMID:17901199</ref><ref>PMID:7643615</ref><ref>PMID:19736320</ref>
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<StructureSection load='2v4z' size='340' side='right'caption='[[2v4z]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2v4z]] is a 2 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=2V4Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V4Z FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2v4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4z OCA], [https://pdbe.org/2v4z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v4z RCSB], [https://www.ebi.ac.uk/pdbsum/2v4z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v4z ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN] Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:[https://omim.org/entry/602483 602483]. ARCND1 is an autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.<ref>PMID:22560091</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(k) is the stimulatory G protein 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.<ref>PMID:17635935</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v4/2v4z_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v4z ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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"Regulator of G-protein signaling" (RGS) proteins facilitate the termination of G protein-coupled receptor (GPCR) signaling via their ability to increase the intrinsic GTP hydrolysis rate of Galpha subunits (known as GTPase-accelerating protein or "GAP" activity). RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits. As many vasoconstrictive hormones signal via G(q) heterotrimer-coupled receptors, it is perhaps not surprising that RGS2-deficient mice exhibit constitutive hypertension. However, to date the particular structural features within RGS2 determining its selectivity for Galpha(q) over Galpha(i/o) substrates have not been completely characterized. Here, we examine a trio of point mutations to RGS2 that elicits Galpha(i)-directed binding and GAP activities without perturbing its association with Galpha(q). Using x-ray crystallography, we determined a model of the triple mutant RGS2 in complex with a transition state mimetic form of Galpha(i) at 2.8-A resolution. Structural comparison with unliganded, wild type RGS2 and of other RGS domain/Galpha complexes highlighted the roles of these residues in wild type RGS2 that weaken Galpha(i) subunit association. Moreover, these three amino acids are seen to be evolutionarily conserved among organisms with modern cardiovascular systems, suggesting that RGS2 arose from the R4-subfamily of RGS proteins to have specialized activity as a potent and selective Galpha(q) GAP that modulates cardiovascular function.
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==About this Structure==
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Structural determinants of G-protein alpha subunit selectivity by regulator of G-protein signaling 2 (RGS2).,Kimple AJ, Soundararajan M, Hutsell SQ, Roos AK, Urban DJ, Setola V, Temple BR, Roth BL, Knapp S, Willard FS, Siderovski DP J Biol Chem. 2009 Jul 17;284(29):19402-11. Epub 2009 May 28. PMID:19478087<ref>PMID:19478087</ref>
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[[2v4z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V4Z OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:019478087</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 2v4z" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Regulator of G-protein signaling 3D structures|Regulator of G-protein signaling 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Large Structures]]
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[[Category: Bountra, C.]]
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[[Category: Arrowsmith CH]]
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[[Category: Edwards, A.]]
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[[Category: Bountra C]]
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[[Category: Knapp, S.]]
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[[Category: Edwards A]]
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[[Category: Pike, A C.W.]]
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[[Category: Knapp S]]
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[[Category: Roos, A K.]]
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[[Category: Pike ACW]]
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[[Category: Soundararajan, M.]]
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[[Category: Roos AK]]
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[[Category: Weigelt, J.]]
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[[Category: Soundararajan M]]
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[[Category: Adp-ribosylation]]
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[[Category: Weigelt J]]
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[[Category: Cell cycle]]
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[[Category: G-protein coupled receptor]]
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[[Category: Gtp hydrolysis]]
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[[Category: Gtp-binding]]
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[[Category: Guanine nucleotide binding protein]]
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[[Category: Lipoprotein]]
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[[Category: Myristate]]
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[[Category: Nucleotide-binding]]
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[[Category: Palmitate]]
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[[Category: Phosphoprotein]]
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[[Category: Signal transduction inhibitor]]
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[[Category: Transducer]]
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[[Category: Transmembrane signaling]]
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Current revision

The crystal structure of the human G-protein subunit alpha (GNAI3) in complex with an engineered regulator of G-protein signaling type 2 domain (RGS2)

PDB ID 2v4z

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