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3ab3

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Revision as of 15:04, 25 December 2014

Crystal structure of p115RhoGEF RGS domain in complex with G alpha 13

Structural highlights

3ab3 is a 4 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:	1zcb
Gene:	Gna13, Gna-13 (Mus musculus), ARHGEF1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[GNAI3_MOUSE] 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. [ARHG1_HUMAN] Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits. Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase. Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain. This GEF activity is inhibited by binding to activated GNA12. Mediates angiotensin-2-induced RhoA activation.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

RH-RhoGEFs are a family of guanine nucleotide exchange factors that contain a regulator of G protein signaling homology (RH) domain. The heterotrimeric G protein Galpha(13) stimulates the guanine nucleotide exchange factor (GEF) activity of RH-RhoGEFs, leading to activation of RhoA. The mechanism by which Galpha(13) stimulates the GEF activity of RH-RhoGEFs, such as p115RhoGEF, has not yet been fully elucidated. Here, specific residues in Galpha(13) that mediate activation of p115RhoGEF are identified. Mutation of these residues significantly impairs binding of Galpha(13) to p115RhoGEF as well as stimulation of GEF activity. These data suggest that the exchange activity of p115RhoGEF is stimulated allosterically by Galpha(13) and not through its interaction with a secondary binding site. A crystal structure of Galpha(13) bound to the RH domain of p115RhoGEF is also presented, which differs from a previously crystallized complex with a Galpha(13)-Galpha(i1) chimera. Taken together, these data provide new insight into the mechanism by which p115RhoGEF is activated by Galpha(13).

Identification of Critical Residues in G{alpha}13 for Stimulation of p115RhoGEF Activity and the Structure of the G{alpha}13-p115RhoGEF Regulator of G Protein Signaling Homology (RH) Domain Complex.,Hajicek N, Kukimoto-Niino M, Mishima-Tsumagari C, Chow CR, Shirouzu M, Terada T, Patel M, Yokoyama S, Kozasa T J Biol Chem. 2011 Jun 10;286(23):20625-36. Epub 2011 Apr 20. PMID:21507947^[5]

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

References

↑ Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P, Bollag G. Identification of a novel guanine nucleotide exchange factor for the Rho GTPase. J Biol Chem. 1996 Oct 11;271(41):25452-8. PMID:8810315
↑ Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC. p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13. Science. 1998 Jun 26;280(5372):2109-11. PMID:9641915
↑ Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G. Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13. Science. 1998 Jun 26;280(5372):2112-4. PMID:9641916
↑ Guilluy C, Bregeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, Henrion D, Scalbert E, Bril A, Torres RM, Offermanns S, Pacaud P, Loirand G. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat Med. 2010 Feb;16(2):183-90. doi: 10.1038/nm.2079. Epub 2010 Jan 24. PMID:20098430 doi:10.1038/nm.2079
↑ Hajicek N, Kukimoto-Niino M, Mishima-Tsumagari C, Chow CR, Shirouzu M, Terada T, Patel M, Yokoyama S, Kozasa T. Identification of Critical Residues in G{alpha}13 for Stimulation of p115RhoGEF Activity and the Structure of the G{alpha}13-p115RhoGEF Regulator of G Protein Signaling Homology (RH) Domain Complex. J Biol Chem. 2011 Jun 10;286(23):20625-36. Epub 2011 Apr 20. PMID:21507947 doi:10.1074/jbc.M110.201392

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ab3"

@@ Line 8: / Line 8: @@
 <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=3ab3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ab3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ab3 RCSB], [http://www.ebi.ac.uk/pdbsum/3ab3 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/GNAI3_MOUSE GNAI3_MOUSE]] 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. [[http://www.uniprot.org/uniprot/ARHG1_HUMAN ARHG1_HUMAN]] Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits. Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase. Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain. This GEF activity is inhibited by binding to activated GNA12. Mediates angiotensin-2-induced RhoA activation.<ref>PMID:8810315</ref> <ref>PMID:9641915</ref> <ref>PMID:9641916</ref> <ref>PMID:20098430</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

3ab3

From Proteopedia

Revision as of 15:04, 25 December 2014

Crystal structure of p115RhoGEF RGS domain in complex with G alpha 13

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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