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2af0

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Revision as of 14:40, 17 November 2021

Structure of the Regulator of G-Protein Signaling Domain of RGS2

Structural highlights

2af0 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4]

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 accelerate GTP hydrolysis by Galpha subunits and thus facilitate termination of signaling initiated by G protein-coupled receptors (GPCRs). RGS proteins hold great promise as disease intervention points, given their signature role as negative regulators of GPCRs-receptors to which the largest fraction of approved medications are currently directed. RGS proteins share a hallmark RGS domain that interacts most avidly with Galpha when in its transition state for GTP hydrolysis; by binding and stabilizing switch regions I and II of Galpha, RGS domain binding consequently accelerates Galpha-mediated GTP hydrolysis. The human genome encodes more than three dozen RGS domain-containing proteins with varied Galpha substrate specificities. To facilitate their exploitation as drug-discovery targets, we have taken a systematic structural biology approach toward cataloging the structural diversity present among RGS domains and identifying molecular determinants of their differential Galpha selectivities. Here, we determined 14 structures derived from NMR and x-ray crystallography of members of the R4, R7, R12, and RZ subfamilies of RGS proteins, including 10 uncomplexed RGS domains and 4 RGS domain/Galpha complexes. Heterogeneity observed in the structural architecture of the RGS domain, as well as in engagement of switch III and the all-helical domain of the Galpha substrate, suggests that unique structural determinants specific to particular RGS protein/Galpha pairings exist and could be used to achieve selective inhibition by small molecules.

Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.,Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundstrom M, Doyle DA, Siderovski DP Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. Epub 2008 Apr 23. PMID:18434541^[5]

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

References

↑ Heximer SP, Lim H, Bernard JL, Blumer KJ. Mechanisms governing subcellular localization and function of human RGS2. J Biol Chem. 2001 Apr 27;276(17):14195-203. Epub 2001 Jan 30. PMID:11278586 doi:10.1074/jbc.M009942200
↑ Gu S, Anton A, Salim S, Blumer KJ, Dessauer CW, Heximer SP. Alternative translation initiation of human regulators of G-protein signaling-2 yields a set of functionally distinct proteins. Mol Pharmacol. 2008 Jan;73(1):1-11. Epub 2007 Sep 27. PMID:17901199 doi:10.1124/mol.107.036285
↑ Wu HK, Heng HH, Shi XM, Forsdyke DR, Tsui LC, Mak TW, Minden MD, Siderovski DP. Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in acute leukemia and localization to human chromosome 1q31. Leukemia. 1995 Aug;9(8):1291-8. PMID:7643615
↑ Nguyen CH, Ming H, Zhao P, Hugendubler L, Gros R, Kimball SR, Chidiac P. Translational control by RGS2. J Cell Biol. 2009 Sep 7;186(5):755-65. PMID:19736320 doi:jcb.200811058
↑ Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundstrom M, Doyle DA, Siderovski DP. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. Epub 2008 Apr 23. PMID:18434541

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2af0"

@@ Line 3: / Line 3: @@
 <StructureSection load='2af0' size='340' side='right'caption='[[2af0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2af0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AF0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2af0]] is a 1 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=2AF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AF0 FirstGlance]. <br>
-</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=2af0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2af0 OCA], [http://pdbe.org/2af0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2af0 RCSB], [http://www.ebi.ac.uk/pdbsum/2af0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2af0 ProSAT]</span></td></tr>
+</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=2af0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2af0 OCA], [https://pdbe.org/2af0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2af0 RCSB], [https://www.ebi.ac.uk/pdbsum/2af0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2af0 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>
+[[https://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]]
@@ Line 27: / Line 27: @@
 </div>
 <div class="pdbe-citations 2af0" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Regulator of G-protein signaling 3D structures|Regulator of G-protein signaling 3D structures]]
 == References ==
 <references/>

2af0

From Proteopedia

Revision as of 14:40, 17 November 2021

Structure of the Regulator of G-Protein Signaling Domain of RGS2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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