4jmf

Structural highlights

Function

EXOT_PSEAE Bifunctional effector protein that is secreted and delivered by the type III secretion system into eukaryotic target cells. The N-terminus encodes a GTPase-activating protein activity, whereas the C-terminus encodes an ADP-ribosyltransferase activity (PubMed:11298647). ADP-ribosylates several eukaryotic proteins including CT10 regulator of kinase (Crk) proteins (PubMed:12807879). In turn, induces atypical anoikis apoptosis by transforming Crk adaptor protein into a cytotoxin (PubMed:26020630). Affects host cell morphology by disrupting the actin cytoskeleton (PubMed:14688136). In addition to this activity, acts via its N-terminal region as a GTPase-activating protein (GAP) for host Rho GTPases including RhoA, Rac1, Cdc42 and Ras (PubMed:11895987). The GAP domain activity induces mitochondrial disruption in the target host cell by activating host caspases 3 and 9 that execute cellular death (PubMed:26451042). This activity also causes stress fiber disassembly (PubMed:11895987).^{[1] [2] [3] [4] [5] [6]}

See Also

• Exoenzyme 3D structures

References

1. ↑ Sundin C, Henriksson ML, Hallberg B, Forsberg A, Frithz-Lindsten E. Exoenzyme T of Pseudomonas aeruginosa elicits cytotoxicity without interfering with Ras signal transduction. Cell Microbiol. 2001 Apr;3(4):237-46. doi: 10.1046/j.1462-5822.2001.00108.x. PMID:11298647 doi:http://dx.doi.org/10.1046/j.1462-5822.2001.00108.x
2. ↑ Kazmierczak BI, Engel JN. Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein for RhoA, Rac1, and Cdc42. Infect Immun. 2002 Apr;70(4):2198-205. doi: 10.1128/IAI.70.4.2198-2205.2002. PMID:11895987 doi:http://dx.doi.org/10.1128/IAI.70.4.2198-2205.2002
3. ↑ Sun J, Barbieri JT. Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 regulator of kinase (Crk) proteins. J Biol Chem. 2003 Aug 29;278(35):32794-800. doi: 10.1074/jbc.M304290200. Epub , 2003 Jun 13. PMID:12807879 doi:http://dx.doi.org/10.1074/jbc.M304290200
4. ↑ Garrity-Ryan L, Shafikhani S, Balachandran P, Nguyen L, Oza J, Jakobsen T, Sargent J, Fang X, Cordwell S, Matthay MA, Engel JN. The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. Infect Immun. 2004 Jan;72(1):546-58. doi: 10.1128/IAI.72.1.546-558.2004. PMID:14688136 doi:http://dx.doi.org/10.1128/IAI.72.1.546-558.2004
5. ↑ Wood S, Goldufsky J, Shafikhani SH. Pseudomonas aeruginosa ExoT Induces Atypical Anoikis Apoptosis in Target Host Cells by Transforming Crk Adaptor Protein into a Cytotoxin. PLoS Pathog. 2015 May 28;11(5):e1004934. doi: 10.1371/journal.ppat.1004934. , eCollection 2015 May. PMID:26020630 doi:http://dx.doi.org/10.1371/journal.ppat.1004934
6. ↑ Wood SJ, Goldufsky JW, Bello D, Masood S, Shafikhani SH. Pseudomonas aeruginosa ExoT Induces Mitochondrial Apoptosis in Target Host Cells in a Manner That Depends on Its GTPase-activating Protein (GAP) Domain Activity. J Biol Chem. 2015 Nov 27;290(48):29063-73. doi: 10.1074/jbc.M115.689950. Epub , 2015 Oct 8. PMID:26451042 doi:http://dx.doi.org/10.1074/jbc.M115.689950