2v4z

From Proteopedia

(Difference between revisions)

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)

Structural highlights

2v4z is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GNAI3_HUMAN Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM: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.^[1]

Function

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.^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

"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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rieder MJ, Green GE, Park SS, Stamper BD, Gordon CT, Johnson JM, Cunniff CM, Smith JD, Emery SB, Lyonnet S, Amiel J, Holder M, Heggie AA, Bamshad MJ, Nickerson DA, Cox TC, Hing AV, Horst JA, Cunningham ML. A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. Am J Hum Genet. 2012 May 4;90(5):907-14. doi: 10.1016/j.ajhg.2012.04.002. PMID:22560091 doi:10.1016/j.ajhg.2012.04.002
↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
↑ Kimple AJ, Soundararajan M, Hutsell SQ, Roos AK, Urban DJ, Setola V, Temple BR, Roth BL, Knapp S, Willard FS, Siderovski DP. Structural determinants of G-protein alpha subunit selectivity by regulator of G-protein signaling 2 (RGS2). J Biol Chem. 2009 Jul 17;284(29):19402-11. Epub 2009 May 28. PMID:19478087 doi:10.1074/jbc.M109.024711

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2v4z"

@@ Line 1: / Line 1: @@
-==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)==
-<StructureSection load='2v4z' size='340' side='right' caption='[[2v4z]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+==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)==
+<StructureSection load='2v4z' size='340' side='right'caption='[[2v4z]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V4Z FirstGlance]. <br>
+<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>
-</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]] 2.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ihb|2ihb]], [[2af0|2af0]]</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=2v4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2v4z RCSB], [http://www.ebi.ac.uk/pdbsum/2v4z PDBsum]</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=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>
 </table>
+== Disease ==
+[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>
 == Function ==
-[[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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v4/2v4z_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v4/2v4z_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2v4z" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Guanine nucleotide-binding protein|Guanine nucleotide-binding protein]]
+*[[Regulator of G-protein signaling 3D structures|Regulator of G-protein signaling 3D structures]]
 == References ==
 <references/>
@@ Line 35: / Line 39: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H]]
+[[Category: Large Structures]]
-[[Category: Bountra, C]]
+[[Category: Arrowsmith CH]]
-[[Category: Edwards, A]]
+[[Category: Bountra C]]
-[[Category: Knapp, S]]
+[[Category: Edwards A]]
-[[Category: Pike, A C.W]]
+[[Category: Knapp S]]
-[[Category: Roos, A K]]
+[[Category: Pike ACW]]
-[[Category: Soundararajan, M]]
+[[Category: Roos AK]]
-[[Category: Weigelt, J]]
+[[Category: Soundararajan M]]
-[[Category: Adp-ribosylation]]
+[[Category: Weigelt J]]
-[[Category: Cell cycle]]
-[[Category: G-protein coupled receptor]]
-[[Category: Gtp hydrolysis]]
-[[Category: Gtp-binding]]
-[[Category: Guanine nucleotide binding protein]]
-[[Category: Lipoprotein]]
-[[Category: Myristate]]
-[[Category: Nucleotide-binding]]
-[[Category: Palmitate]]
-[[Category: Phosphoprotein]]
-[[Category: Signal transduction inhibitor]]
-[[Category: Transducer]]
-[[Category: Transmembrane signaling]]

2v4z

From Proteopedia

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)

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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