1tx4

From Proteopedia

(Difference between revisions)

Revision as of 09:33, 29 September 2021

RHO/RHOGAP/GDP(DOT)ALF4 COMPLEX

Structural highlights

1tx4 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RHG01_HUMAN] GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate. [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

Small G proteins of the Rho family, which includes Rho, Rac and Cdc42Hs, regulate phosphorylation pathways that control a range of biological functions including cytoskeleton formation and cell proliferation. They operate as molecular switches, cycling between the biologically active GTP-bound form and the inactive GDP-bound state. Their rate of hydrolysis of GTP to GDP by virtue of their intrinsic GTPase activity is slow, but can be accelerated by up to 10(5)-fold through interaction with rhoGAP, a GTPase-activating protein that stimulates Rho-family proteins. As such, rhoGAP plays a crucial role in regulating Rho-mediated signalling pathways. Here we report the crystal structure of RhoA and rhoGAP complexed with the transition-state analogue GDP.AlF4- at 1.65 A resolution. There is a rotation of 20 degrees between the Rho and rhoGAP proteins in this complex when compared with the ground-state complex Cdc42Hs.GMPPNP/rhoGAP, in which Cdc42Hs is bound to the non-hydrolysable GTP analogue GMPPNP. Consequently, in the transition state complex but not in the ground state, the rhoGAP domain contributes a residue, Arg85(GAP) directly into the active site of the G protein. We propose that this residue acts to stabilize the transition state of the GTPase reaction. RhoGAP also appears to function by stabilizing several regions of RhoA that are important in signalling the hydrolysis of GTP.

Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue.,Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ Nature. 1997 Oct 16;389(6652):758-62. PMID:9338791^[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
↑ Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ. Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue. Nature. 1997 Oct 16;389(6652):758-62. PMID:9338791 doi:10.1038/39651

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/1tx4"

@@ Line 3: / Line 3: @@
 <StructureSection load='1tx4' size='340' side='right'caption='[[1tx4]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1tx4]] is a 2 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=1TX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TX4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1tx4]] is a 2 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=1TX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TX4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=1tx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tx4 OCA], [http://pdbe.org/1tx4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tx4 RCSB], [http://www.ebi.ac.uk/pdbsum/1tx4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tx4 ProSAT]</span></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=1tx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tx4 OCA], [https://pdbe.org/1tx4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tx4 RCSB], [https://www.ebi.ac.uk/pdbsum/1tx4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tx4 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/RHG01_HUMAN RHG01_HUMAN]] GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate. [[http://www.uniprot.org/uniprot/RHOA_HUMAN 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.<ref>PMID:8910519</ref> <ref>PMID:9121475</ref> <ref>PMID:12900402</ref> <ref>PMID:16103226</ref> <ref>PMID:16236794</ref> <ref>PMID:19934221</ref> <ref>PMID:20937854</ref> <ref>PMID:20974804</ref>
+[[https://www.uniprot.org/uniprot/RHG01_HUMAN RHG01_HUMAN]] GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate. [[https://www.uniprot.org/uniprot/RHOA_HUMAN 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.<ref>PMID:8910519</ref> <ref>PMID:9121475</ref> <ref>PMID:12900402</ref> <ref>PMID:16103226</ref> <ref>PMID:16236794</ref> <ref>PMID:19934221</ref> <ref>PMID:20937854</ref> <ref>PMID:20974804</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1tx4

From Proteopedia

Revision as of 09:33, 29 September 2021

RHO/RHOGAP/GDP(DOT)ALF4 COMPLEX

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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