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5efx

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Revision as of 06:56, 22 April 2020

Crystal structure of Rho GTPase regulator

Structural highlights

5efx 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.
Gene:	ARHGEF2, KIAA0651, LFP40 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ARHG2_HUMAN] Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2) is identified as a member of the Dbl family of GEFs. It regulates RhoA-dependent cell signaling pathways and plays important roles in biological processes. GEF-H1 contains an N-terminal zinc finger domain, a Dbl-homologous (DH) domain followed by a Pleckstrin homology (PH) domain, and a C-terminal domain. The specific roles of its PH domain are poorly understood. Here we report the crystal structure of human GEF-H1 PH domain to 2.45 A resolution. A conserved surface is formed by beta8, beta9, beta10, and it may mediate protein-protein interactions. Although the folding resembles other PH domains that have defined structures, superposition of different PH domains clearly shows that the loop between beta6/beta7 and the loop between beta3/beta4 are so close that they will prevent its binding with phosphoinositide due to steric hindrance, and this has been proved by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). Our studies provide a structural framework for further work on the function of GEF-H1.

Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding.,Jiang Y, Jiang H, Zhou S, Meng B, Liu ZJ, Ouyang S Biochem Biophys Res Commun. 2016 Mar 18;471(4):621-7. doi:, 10.1016/j.bbrc.2016.01.150. Epub 2016 Jan 26. PMID:26820534^[4]

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

References

↑ Fukazawa A, Alonso C, Kurachi K, Gupta S, Lesser CF, McCormick BA, Reinecker HC. GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. PLoS Pathog. 2008 Nov;4(11):e1000228. doi: 10.1371/journal.ppat.1000228. Epub, 2008 Nov 28. PMID:19043560 doi:10.1371/journal.ppat.1000228
↑ Zhao Y, Alonso C, Ballester I, Song JH, Chang SY, Guleng B, Arihiro S, Murray PJ, Xavier R, Kobayashi KS, Reinecker HC. Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. Inflamm Bowel Dis. 2012 Apr;18(4):603-12. doi: 10.1002/ibd.21851. Epub 2011 Sep, 1. PMID:21887730 doi:http://dx.doi.org/10.1002/ibd.21851
↑ Ren Y, Li R, Zheng Y, Busch H. Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. J Biol Chem. 1998 Dec 25;273(52):34954-60. PMID:9857026
↑ Jiang Y, Jiang H, Zhou S, Meng B, Liu ZJ, Ouyang S. Crystal structure of hGEF-H1 PH domain provides insight into incapability in phosphoinositide binding. Biochem Biophys Res Commun. 2016 Mar 18;471(4):621-7. doi:, 10.1016/j.bbrc.2016.01.150. Epub 2016 Jan 26. PMID:26820534 doi:http://dx.doi.org/10.1016/j.bbrc.2016.01.150

1 Structural highlights
2 Function
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/5efx"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Rho GTPase regulator==
-<StructureSection load='5efx' size='340' side='right' caption='[[5efx]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
+<StructureSection load='5efx' size='340' side='right'caption='[[5efx]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5efx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EFX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EFX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5efx]] 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=5EFX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EFX 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=5efx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efx OCA], [http://pdbe.org/5efx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efx RCSB], [http://www.ebi.ac.uk/pdbsum/5efx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5efx ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARHGEF2, KIAA0651, LFP40 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5efx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5efx OCA], [http://pdbe.org/5efx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5efx RCSB], [http://www.ebi.ac.uk/pdbsum/5efx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5efx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 </div>
 <div class="pdbe-citations 5efx" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Jiang, Y]]
 [[Category: Liu, Z J]]

5efx

From Proteopedia

Revision as of 06:56, 22 April 2020

Crystal structure of Rho GTPase regulator

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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