1xcg

From Proteopedia

(Difference between revisions)

Revision as of 09:53, 6 January 2021

Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF

Structural highlights

1xcg is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	ARHGEF11, KIAA0380 (HUMAN), RHOA, ARHA, ARH12, RHO12 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ARHGB_HUMAN] May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. [RHOA_HUMAN] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

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

Calcium sensitization in smooth muscle is mediated by the RhoA GTPase, activated by hitherto unspecified nucleotide exchange factors (GEFs) acting downstream of Galphaq/Galpha(12/13) trimeric G proteins. Here, we show that at least one potential GEF, the PDZRhoGEF, is present in smooth muscle, and its isolated DH/PH fragment induces calcium sensitization in the absence of agonist-mediated signaling. In vitro, the fragment shows high selectivity for the RhoA GTPase. Full-length fragment is required for the nucleotide exchange, as the isolated DH domain enhances it only marginally. We crystallized the DH/PH fragment of PDZRhoGEF in complex with nonprenylated human RhoA and determined the structure at 2.5 A resolution. The refined molecular model reveals that the mutual disposition of the DH and PH domains is significantly different from other previously described complexes involving DH/PH tandems, and that the PH domain interacts with RhoA in a unique mode. The DH domain makes several specific interactions with RhoA residues not conserved among other Rho family members, suggesting the molecular basis for the observed specificity.

The crystal structure of RhoA in complex with the DH/PH fragment of PDZRhoGEF, an activator of the Ca(2+) sensitization pathway in smooth muscle.,Derewenda U, Oleksy A, Stevenson AS, Korczynska J, Dauter Z, Somlyo AP, Otlewski J, Somlyo AV, Derewenda ZS Structure. 2004 Nov;12(11):1955-65. PMID:15530360^[9]

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

References

↑ Quilliam LA, Lambert QT, Mickelson-Young LA, Westwick JK, Sparks AB, Kay BK, Jenkins NA, Gilbert DJ, Copeland NG, Der CJ. Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling. J Biol Chem. 1996 Nov 15;271(46):28772-6. PMID:8910519
↑ Vincent S, Settleman J. The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol Cell Biol. 1997 Apr;17(4):2247-56. PMID:9121475
↑ Wing MR, Snyder JT, Sondek J, Harden TK. Direct activation of phospholipase C-epsilon by Rho. J Biol Chem. 2003 Oct 17;278(42):41253-8. Epub 2003 Aug 4. PMID:12900402 doi:http://dx.doi.org/10.1074/jbc.M306904200
↑ Yuce O, Piekny A, Glotzer M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005 Aug 15;170(4):571-82. PMID:16103226 doi:10.1083/jcb.200501097
↑ Kamijo K, Ohara N, Abe M, Uchimura T, Hosoya H, Lee JS, Miki T. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006 Jan;17(1):43-55. Epub 2005 Oct 19. PMID:16236794 doi:10.1091/mbc.E05-06-0569
↑ Bristow JM, Sellers MH, Majumdar D, Anderson B, Hu L, Webb DJ. The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration. J Cell Sci. 2009 Dec 15;122(Pt 24):4535-46. doi: 10.1242/jcs.053728. Epub 2009, Nov 24. PMID:19934221 doi:10.1242/jcs.053728
↑ Zaoui K, Benseddik K, Daou P, Salaun D, Badache A. ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18517-22. doi:, 10.1073/pnas.1000975107. Epub 2010 Oct 11. PMID:20937854 doi:10.1073/pnas.1000975107
↑ Wallace SW, Magalhaes A, Hall A. The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells. Mol Cell Biol. 2011 Jan;31(1):81-91. doi: 10.1128/MCB.01001-10. Epub 2010 Oct 25. PMID:20974804 doi:10.1128/MCB.01001-10
↑ Derewenda U, Oleksy A, Stevenson AS, Korczynska J, Dauter Z, Somlyo AP, Otlewski J, Somlyo AV, Derewenda ZS. The crystal structure of RhoA in complex with the DH/PH fragment of PDZRhoGEF, an activator of the Ca(2+) sensitization pathway in smooth muscle. Structure. 2004 Nov;12(11):1955-65. PMID:15530360 doi:10.1016/j.str.2004.09.003

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xcg"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF==
-<StructureSection load='1xcg' size='340' side='right' caption='[[1xcg]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='1xcg' size='340' side='right'caption='[[1xcg]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1xcg]] is a 4 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=1XCG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XCG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1xcg]] is a 4 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=1XCG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1XCG FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARHGEF11, KIAA0380 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RHOA, ARHA, ARH12, RHO12 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xcg OCA], [http://pdbe.org/1xcg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xcg RCSB], [http://www.ebi.ac.uk/pdbsum/1xcg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xcg ProSAT]</span></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=1xcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xcg OCA], [http://pdbe.org/1xcg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xcg RCSB], [http://www.ebi.ac.uk/pdbsum/1xcg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xcg ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 30: / Line 30: @@
 ==See Also==
-*[[Rho GTPase|Rho GTPase]]
+*[[Rho GTPase 3D structures|Rho GTPase 3D structures]]
-*[[Rho guanine nucleotide exchange factor|Rho guanine nucleotide exchange factor]]
+*[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Dauter, Z]]
 [[Category: Derewenda, U]]

1xcg

From Proteopedia

Revision as of 09:53, 6 January 2021

Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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