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2p2l

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Revision as of 09:16, 18 October 2017

Rac1-GDP-Zinc Complex

Structural highlights

2p2l is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	RAC1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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

The Rho family of small GTPases represent well characterized signaling molecules that regulate many cellular functions such as actin cytoskeletal arrangement and the cell cycle by acting as molecular switches. A Rac1-GDP-Zn complex has been crystallized in space group P3(2)21 and its crystal structure has been solved at 1.9 A resolution. These trigonal crystals reveal the unexpected ability of Rac1 to coordinate Zn atoms in a tetrahedral fashion by use of its biologically relevant switch I and switch II regions. Upon coordination of zinc, the switch I region is stabilized in the GDP-bound conformation and contributes to a Rac1 trimer in the asymmetric unit. Zinc coordination causes switch II to adopt a novel conformation with a symmetry-related molecule. Additionally, zinc was found to displace magnesium from its octahedral coordination at switch I, although GDP binding remained stable. This structure represents the first reported Rac1-GDP-Zn complex, which further underscores the conformational flexibility and versatility of the small GTPase switch regions.

A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium.,Prehna G, Stebbins CE Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):628-35. Epub 2007, Apr 21. PMID:17452788^[11]

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

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
↑ Prehna G, Stebbins CE. A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium. Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):628-35. Epub 2007, Apr 21. PMID:17452788 doi:10.1107/S0907444907010888

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/2p2l"

Categories: Human | Prehna, G | Stebbins, C E | Rho family gtpase | Unknown function

@@ Line 1: / Line 1: @@
 ==Rac1-GDP-Zinc Complex==
 <StructureSection load='2p2l' size='340' side='right' caption='[[2p2l]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAC1 ([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=2p2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p2l OCA], [http://pdbe.org/2p2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p2l RCSB], [http://www.ebi.ac.uk/pdbsum/2p2l PDBsum]</span></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=2p2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p2l OCA], [http://pdbe.org/2p2l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p2l RCSB], [http://www.ebi.ac.uk/pdbsum/2p2l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p2l ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 29: @@
 </div>
 <div class="pdbe-citations 2p2l" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Rac|Rac]]
 == References ==
 <references/>

2p2l

From Proteopedia

Revision as of 09:16, 18 October 2017

Rac1-GDP-Zinc Complex

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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