| Structural highlights
4ekd is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Related: | 1agr, 2v4z, 2af0, 2bcj, 4ekc |
| Gene: | Gnaq (Mus musculus), RGS2, G0S8, GIG31 (Homo sapiens) |
| Activity: | Heterotrimeric G-protein GTPase, with EC number 3.6.5.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[GNAQ_MOUSE] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro).[1] [2] [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.[3] [4] [5] [6]
Publication Abstract from PubMed
The heterotrimeric G protein Galphaq is a key regulator of blood pressure, and excess Galphaq signaling leads to hypertension. A specific inhibitor of Galphaq is the GTPase activating protein (GAP) known as regulator of G protein signaling 2 (RGS2). The molecular basis for how Galphaq/11 subunits serve as substrates for RGS proteins and how RGS2 mandates its selectivity for Galphaq is poorly understood. In crystal structures of the RGS2-Galphaq complex, RGS2 docks to Galphaq in a different orientation from that observed in RGS-Galphai/o complexes. Despite its unique pose, RGS2 maintains canonical interactions with the switch regions of Galphaq in part because its alpha6 helix adopts a distinct conformation. We show that RGS2 forms extensive interactions with the alpha-helical domain of Galphaq that contribute to binding affinity and GAP potency. RGS subfamilies that do not serve as GAPs for Galphaq are unlikely to form analogous stabilizing interactions.
Structural and functional analysis of the regulator of G protein signaling 2-galphaq complex.,Nance MR, Kreutz B, Tesmer VM, Sterne-Marr R, Kozasa T, Tesmer JJ Structure. 2013 Mar 5;21(3):438-48. doi: 10.1016/j.str.2012.12.016. Epub 2013 Feb, 21. PMID:23434405[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shi G, Partida-Sanchez S, Misra RS, Tighe M, Borchers MT, Lee JJ, Simon MI, Lund FE. Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. J Exp Med. 2007 Oct 29;204(11):2705-18. Epub 2007 Oct 15. PMID:17938235 doi:10.1084/jem.20071267
- ↑ Misra RS, Shi G, Moreno-Garcia ME, Thankappan A, Tighe M, Mousseau B, Kusser K, Becker-Herman S, Hudkins KL, Dunn R, Kehry MR, Migone TS, Marshak-Rothstein A, Simon M, Randall TD, Alpers CE, Liggitt D, Rawlings DJ, Lund FE. G alpha q-containing G proteins regulate B cell selection and survival and are required to prevent B cell-dependent autoimmunity. J Exp Med. 2010 Aug 2;207(8):1775-89. doi: 10.1084/jem.20092735. Epub 2010 Jul, 12. PMID:20624888 doi:10.1084/jem.20092735
- ↑ 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
- ↑ Nance MR, Kreutz B, Tesmer VM, Sterne-Marr R, Kozasa T, Tesmer JJ. Structural and functional analysis of the regulator of G protein signaling 2-galphaq complex. Structure. 2013 Mar 5;21(3):438-48. doi: 10.1016/j.str.2012.12.016. Epub 2013 Feb, 21. PMID:23434405 doi:10.1016/j.str.2012.12.016
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