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2v4z

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Revision as of 06:29, 4 April 2018

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 Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2ihb, 2af0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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^[1]

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

References

↑ 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 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 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)==
+==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 ==
@@ Line 5: / Line 6: @@
 </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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ihb|2ihb]], [[2af0|2af0]]</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://pdbe.org/2v4z PDBe], [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'>[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://pdbe.org/2v4z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v4z RCSB], [http://www.ebi.ac.uk/pdbsum/2v4z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2v4z ProSAT]</span></td></tr>
 </table>
-== 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>
 == 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>
@@ Line 30: / Line 29: @@
 ==See Also==
-*[[Guanine nucleotide-binding protein|Guanine nucleotide-binding protein]]
+*[[Regulator of G protein signaling|Regulator of G protein signaling]]
 == References ==
 <references/>

2v4z

From Proteopedia

Revision as of 06:29, 4 April 2018

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

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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