| Structural highlights
Function
[SPTP_SALTY] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein includes tyrosine phosphatase and GTPase activating protein (GAP) activities. After bacterial internalization, GAP mediates the reversal of the cytoskeletal changes induced by SopE. This function is independent of its tyrosine phosphatase activity, which remains unclear.[1] [2] [3] [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.[4] [5] [6] [7] [8] 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.[9] [10] [11] [12] [13]
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
Salmonella spp. utilize a specialized protein secretion system to deliver a battery of effector proteins into host cells. Several of these effectors stimulate Cdc42- and Rac1-dependent cytoskeletal changes that promote bacterial internalization. These potentially cytotoxic alterations are rapidly reversed by the effector SptP, a tyrosine phosphatase and GTPase activating protein (GAP) that targets Cdc42 and Rac1. The 2.3 A resolution crystal structure of an SptP-Rac1 transition state complex reveals an unusual GAP architecture that mimics host functional homologs. The phosphatase domain possesses a conserved active site but distinct surface properties. Binding to Rac1 induces a dramatic stabilization in SptP of a four-helix bundle that makes extensive contacts with the Switch I and Switch II regions of the GTPase.
Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1.,Stebbins CE, Galan JE Mol Cell. 2000 Dec;6(6):1449-60. PMID:11163217[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kaniga K, Uralil J, Bliska JB, Galan JE. A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurium. Mol Microbiol. 1996 Aug;21(3):633-41. PMID:8866485
- ↑ Fu Y, Galan JE. A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature. 1999 Sep 16;401(6750):293-7. PMID:10499590 doi:http://dx.doi.org/10.1038/45829
- ↑ Stebbins CE, Galan JE. Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol Cell. 2000 Dec;6(6):1449-60. PMID:11163217
- ↑ 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
- ↑ Stebbins CE, Galan JE. Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol Cell. 2000 Dec;6(6):1449-60. PMID:11163217
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