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| ==A Complex between PH Domain of p190RhoGEF and Activated Rac1 Bound to a GTP Analog== | | ==A Complex between PH Domain of p190RhoGEF and Activated Rac1 Bound to a GTP Analog== |
- | <StructureSection load='6bc1' size='340' side='right' caption='[[6bc1]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='6bc1' size='340' side='right'caption='[[6bc1]], [[Resolution|resolution]] 2.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6bc1]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BC1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BC1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bc1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BC1 FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</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=6bc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bc1 OCA], [http://pdbe.org/6bc1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bc1 RCSB], [http://www.ebi.ac.uk/pdbsum/6bc1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bc1 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSP:5-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</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'>[https://proteopedia.org/fgij/fg.htm?mol=6bc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bc1 OCA], [https://pdbe.org/6bc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bc1 RCSB], [https://www.ebi.ac.uk/pdbsum/6bc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bc1 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/RAC1_HUMAN RAC1_HUMAN]] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> [[http://www.uniprot.org/uniprot/ARG28_HUMAN ARG28_HUMAN]] Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Functions also in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis (By similarity). | + | [https://www.uniprot.org/uniprot/RAC1_HUMAN RAC1_HUMAN] Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.<ref>PMID:1643658</ref> <ref>PMID:9121475</ref> <ref>PMID:19934221</ref> <ref>PMID:19403692</ref> <ref>PMID:20696765</ref> |
| + | |
| + | ==See Also== |
| + | *[[Rac 3D structures|Rac 3D structures]] |
| + | *[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Chen, Z]] | + | [[Category: Homo sapiens]] |
- | [[Category: Sternweis, P C]] | + | [[Category: Large Structures]] |
- | [[Category: Rho gtpase guanine nucleotide exchange factors rhogef pleckstrin homology ph domain]] | + | [[Category: Chen Z]] |
- | [[Category: Signaling protein]] | + | [[Category: Sternweis PC]] |
| Structural highlights
Function
RAC1_HUMAN Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion.[1] [2] [3] [4] [5] Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.[6] [7] [8] [9] [10]
See Also
References
- ↑ Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992 Aug 7;70(3):401-10. PMID:1643658
- ↑ 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
- ↑ 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
- ↑ Hamill KJ, Hopkinson SB, DeBiase P, Jones JC. BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated modulation of Rac1 and cofilin activities. Mol Biol Cell. 2009 Jun;20(12):2954-62. doi: 10.1091/mbc.E09-01-0051. Epub 2009, Apr 29. PMID:19403692 doi:10.1091/mbc.E09-01-0051
- ↑ Li X, Lee AY. Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase. J Biol Chem. 2010 Oct 15;285(42):32436-45. doi: 10.1074/jbc.M110.120451. Epub, 2010 Aug 9. PMID:20696765 doi:10.1074/jbc.M110.120451
- ↑ Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992 Aug 7;70(3):401-10. PMID:1643658
- ↑ 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
- ↑ 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
- ↑ Hamill KJ, Hopkinson SB, DeBiase P, Jones JC. BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated modulation of Rac1 and cofilin activities. Mol Biol Cell. 2009 Jun;20(12):2954-62. doi: 10.1091/mbc.E09-01-0051. Epub 2009, Apr 29. PMID:19403692 doi:10.1091/mbc.E09-01-0051
- ↑ Li X, Lee AY. Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase. J Biol Chem. 2010 Oct 15;285(42):32436-45. doi: 10.1074/jbc.M110.120451. Epub, 2010 Aug 9. PMID:20696765 doi:10.1074/jbc.M110.120451
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