Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors

Nature Reviews Microbiology

Volumn 11, Issue 5, 2013, Pages 316-326

  Hicks, Stuart W ^a   Galán, Jorge E ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL EFFECTOR PROTEIN; BACTERIAL PROTEIN; PHOSPHATIDYLINOSITIDE; PHOSPHOLIPID BINDING PROTEIN; UNCLASSIFIED DRUG;

BACTERIAL SECRETION SYSTEM; CELL MEMBRANE; CELL NUCLEUS; CELLULAR DISTRIBUTION; CHLOROPLAST; ESCHERICHIA COLI; EUKARYOTIC CELL; FLAGELLUM; HELICOBACTER PYLORI; HOST CELL; HOST PATHOGEN INTERACTION; LEGIONELLA PNEUMOPHILA; LIPOGENESIS; MITOCHONDRION; MYRISTYLATION; NONHUMAN; PALMITOYLATION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PRENYLATION; PROTEIN STABILITY; PROTEIN TARGETING; PROTEIN TRANSPORT; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS SYRINGAE; REVIEW; RHIZOBIUM RADIOBACTER; SALMONELLA ENTERICA; SEQUENCE ANALYSIS; TARGET CELL; TYPE III SECRETION SYSTEM; TYPE IV SECRETION SYSTEM; UBIQUITINATION;

BACTERIA; BACTERIAL PROTEINS; BACTERIAL SECRETION SYSTEMS; FATTY ACIDS, MONOUNSATURATED; HOST-PATHOGEN INTERACTIONS; LIPOYLATION; MEMBRANE PROTEINS; PRENYLATION;

BACTERIA (MICROORGANISMS); EUKARYOTA;

EID: 84876391962     PISSN: 17401526     EISSN: 17401534     Source Type: Journal    
DOI: 10.1038/nrmicro3009     Document Type: Review

References (125)

1. Christie, P., Atmakuri, K., Krishnamoorthy, V., Jakubowski, S. & Cascales, E. Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu. Rev. Microbiol. 59, 451-485 (2005).
2. Galán, J. E. & Wolf-Watz, H. Protein delivery into eukaryotic cells by type III secretion machines. Nature 444, 567-573 (2006).
3. Galán, J. Common themes in the design and function of bacterial effectors. Cell Host Microbe 5, 571-579 (2009).
4. Ashida, H. et al. A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKγ to dampen the host NF-κB-mediated inflammatory response. Nature Cell Biol. 12, 66-73 (2010).
5. Xin, D. W. et al. Functional analysis of NopM, a novel E3 ubiquitin ligase (NEL) domain effector of Rhizobium sp. strain NGR234. PLoS Pathog. 8, e1002707 (2012).
6. Linder, M. E. & Deschenes, R. J. Palmitoylation: policing protein stability and traffic. Nature Rev. Mol. Cell Biol. 8, 74-84 (2007).
7. Resh, M. D. Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci. STKE 2006, re14 (2006).
8. Smotrys, J. E. & Linder, M. E. Palmitoylation of intracellular signaling proteins: regulation and function. Annu. Rev. Biochem. 73, 559-587 (2004).
9. Greaves, J. & Chamberlain, L. H. Palmitoylation-dependent protein sorting. J. Cell Biol. 176, 249-254 (2007).
10. Hicks, S. W., Charron, G., Hang, H. C. & Galán, J. E. Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation. Cell Host Microbe 10, 9-20 (2011).
11. Quezada, C. M., Hicks, S. W., Galán, J. E. & Stebbins, C. E. A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases. Proc. Natl Acad. Sci. USA 106, 4864-4869 (2009).
12. Hicks, S. W. & Galán, J. E. Hijacking the host ubiquitin pathway: structural strategies of bacterial E3 ubiquitin ligases. Curr. Opin. Microbiol. 13, 41-46 (2010).
13. McLaughlin, L. M. et al. The Salmonella SPI2 effector SseI mediates long-term systemic infection by modulating host cell migration. PLoS Pathog. 5, e1000671 (2009).
14. Worley, M. J., Nieman, G. S., Geddes, K. & Heffron, F. Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells. Proc. Natl Acad. Sci. USA 103, 17915-17920 (2006).
15. Farazi, T. A., Waksman, G. & Gordon, J. I. The biology and enzymology of protein N-myristoylation. J. Biol. Chem. 276, 39501-39504 (2001).
16. Towler, D. A., Eubanks, S. R., Towery, D. S., Adams, S. P. & Glaser, L. Amino-terminal processing of proteins by N-myristoylation. Substrate specificity of N-myristoyl transferase. J. Biol. Chem. 262, 1030-1036 (1987).
17. Block, A. & Alfano, J. Plant targets for Pseudomonas syringae type III effectors: virulence targets or guarded decoys? Curr. Opin. Microbiol. 14, 39-46 (2011).
18. Feng, F. & Zhou, J. Plant-bacterial pathogen interactions mediated by type III effectors. Curr. Opin. Plant Biol. 15, 469-476 (2012).
19. Nimchuk, Z. et al. Eukaryotic fatty acylation drives plasma membrane targeting and enhances function of several type III effector proteins from Pseudomonas syringae. Cell 101, 353-363 (2000).
20. Lewis, J. D., Abada, W., Ma, W., Guttman, D. S. & Desveaux, D. The HopZ family of Pseudomonas syringae type III effectors require myristoylation for virulence and avirulence functions in Arabidopsis thaliana. J. Bacteriol. 190, 2880-2891 (2008).
21. Robert-Seilaniantz, A., Shan, L., Zhou, J. M. & Tang, X. The Pseudomonas syringae pv. tomato DC3000 type III effector HopF2 has a putative myristoylation site required for its avirulence and virulence functions. Mol. Plant Microbe Interact. 19, 130-138 (2006).
22. Thornbrough, J. M. & Worley, M. J. A naturally occurring single nucleotide polymorphism in the Salmonella SPI-2 type III effector srfH/sseI controls early extraintestinal dissemination. PLoS ONE 7, e45245 (2012).
23. Marathe, R. & Dinesh-Kumar, S. P. Plant defense: one post, multiple guards?! Mol. Cell 11, 284-286 (2003).
24. Dowen, R. H., Engel, J. L., Shao, F., Ecker, J. R. & Dixon, J. E. A family of bacterial cysteine protease type III effectors utilizes acylation-dependent and-independent strategies to localize to plasma membranes. J. Biol. Chem. 284, 15867-15879 (2009).
25. Martin, D. D., Beauchamp, E. & Berthiaume, L. G. Post-translational myristoylation: fat matters in cellular life and death. Biochimie 93, 18-31 (2011).
26. Shao, F. et al. Cleavage of Arabidopsis PBS1 by a bacterial type III effector. Science 301, 1230-1233 (2003).
27. Shao, F., Merritt, P. M., Bao, Z., Innes, R. W. & Dixon, J. E. A. Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell 109, 575-588 (2002).
28. Zhang, F. L. & Casey, P. J. Protein prenylation: molecular mechanisms and functional consequences. Annu. Rev. Biochem. 65, 241-269 (1996).
29. Boyartchuk, V. L., Ashby, M. N. & Rine, J. Modulation of Ras and a-factor function by carboxyl-terminal proteolysis. Science 275, 1796-1800 (1997).
30. Dai, Q. et al. Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum. J. Biol. Chem. 273, 15030-15034 (1998).
31. Ivanov, S. S., Charron, G., Hang, H. C. & Roy, C. R. Lipidation by the host prenyltransferase machinery facilitates membrane localization of Legionella pneumophila effector proteins. J. Biol. Chem. 285, 34686-34698 (2010).
32. Price, C. T., Al-Quadan, T., Santic, M., Jones, S. C. & Abu Kwaik, Y. Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila. J. Exp. Med. 207, 1713-1726 (2010).
33. Price, C. T., Jones, S. C., Amundson, K. E. & Kwaik, Y. A. Host-mediated post-translational prenylation of novel Dot/Icm-translocated effectors of Legionella pneumophila. Front. Microbiol. 1, 131 (2010).
34. Reinicke, A. T. et al. A Salmonella typhimurium effector protein SifA is modified by host cell prenylation and S-acylation machinery. J. Biol. Chem. 280, 14620-14627 (2005).
35. Boucrot, E., Beuzon, C. R., Holden, D. W., Gorvel, J. P. & Meresse, S. Salmonella typhimurium SifA effector protein requires its membrane-anchoring C-terminal hexapeptide for its biological function. J. Biol. Chem. 278, 14196-14202 (2003).
36. Stein, M. A., Leung, K. Y., Zwick, M., Garcia-del Portillo, F. & Finlay, B. B. Identification of a Salmonella virulence gene required for formation of filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Mol. Microbiol. 20, 151-164 (1996).
37. Kerscher, O., Felberbaum, R. & Hochstrasser, M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu. Rev. Cell Dev. Biol. 22, 159-180 (2006).
38. Ikeda, F. & Dikic, I. Atypical ubiquitin chains: new molecular signals. EMBO Rep. 9, 536-542 (2008).
39. Haglund, K. & Dikic, I. Ubiquitylation and cell signaling. EMBO J. 24, 3353-3359 (2005).
40. Hicke, L. & Dunn, R. Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu. Rev. Cell Dev. Biol. 19, 141-172 (2003).
41. Huang, J., Xu, L. G., Liu, T., Zhai, Z. & Shu, H. B. The p53-inducible E3 ubiquitin ligase p53RFP induces p53-dependent apoptosis. FEBS Lett. 580, 940-947 (2006).
42. Thrower, J. S., Hoffman, L., Rechsteiner, M. & Pickart, C. M. Recognition of the polyubiquitin proteolytic signal. EMBO J. 19, 94-102 (2000).
43. Xu, P. et al. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137, 133-145 (2009).
44. Kubori, T. & Nagai, H. Bacterial effector-involved temporal and spatial regulation by hijack of the host ubiquitin pathway. Front. Microbiol. 2, 145 (2011).
45. Collins, C. A. & Brown, E. J. Cytosol as battleground: ubiquitin as a weapon for both host and pathogen. Trends Cell Biol. 20, 205-213 (2010).
46. Kubori, T. & Galan, J. E. Temporal regulation of Salmonella virulence effector function by proteasome-dependent protein degradation. Cell 11 5, 333-342 (2003).
47. Kubori, T., Shinzawa, N., Kanuka, H. & Nagai, H. Legionella metaeffector exploits host proteasome to temporally regulate cognate effector. PLoS Pathog. 6, e1001216 (2010).
48. Patel, J. C. & Galán, J. E. Differential activation and function of Rho GTPases during Salmonella-host cell interactions. J. Cell Biol. 175, 453-463 (2006).
49. Steele-Mortimer, O. et al. Activation of Akt/protein kinase B in epithelial cells by the Salmonella typhimurium effector SigD. J. Biol. Chem. 275, 37718-37724 (2000).
50. Hernandez, L. D., Hueffer, K., Wenk, M. R. & Galán, J. E. Salmonella modulates vesicular traffic by altering phosphoinositide metabolism. Science 304, 1805-1807 (2004).
51. Knodler, L. A., Winfree, S., Drecktrah, D., Ireland, R. & Steele-Mortimer, O. Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane. Cell. Microbiol. 11, 1652-1670 (2009).
52. Patel, J. C, Hueffer, K., Lam, T. T. & Galán, J. E. Diversification of a Salmonella virulence protein function by ubiquitin-dependent differential localization. Cell 137, 283-294 (2009).
53. Sorkin, A. & Goh, L. K. Endocytosis and intracellular trafficking of ErbBs. Exp. Cell Res. 315, 683-696 (2009).
54. von Zastrow, M. & Sorkin, A. Signaling on the endocytic pathway. Curr. Opin. Cell Biol. 19, 436-445 (2007).
55. De Matteis, M. A. & Godi, A. PI-loting membrane traffic. Nature Cell Biol. 6, 487-492 (2004).
56. Di Paolo, G. & De Camilli, P. Phosphoinositides in cell regulation and membrane dynamics. Nature 443, 651-657 (2006).
57. Michell, R. H. Inositol derivatives: evolution and functions. Nature Rev. Mol. Cell Biol. 9, 151-161 (2008).
58. Pizarro-Cerda, J. & Cossart, P. Subversion of phosphoinositide metabolism by intracellular bacterial pathogens. Nature Cell Biol. 6, 1026-1033 (2004).
59. Weber, S. S., Ragaz, C. & Hilbi, H. Pathogen trafficking pathways and host phosphoinositide metabolism. Mol. Microbiol. 71, 1341-1352 (2009).
60. Weber, S. S., Ragaz, C, Reus, K., Nyfeler, Y. & Hilbi, H. Legionella pneumophila exploits PI(4)P to anchor secreted effector proteins to the replicative vacuole. PLoS Pathog. 2, e46 (2006).
61. Ragaz, C. et al. The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replication-permissive vacuole. Cell. Microbiol. 10, 2416-2433 (2008).
62. Brombacher, E. et al. Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphate-binding effector protein of Legionella pneumophila. J. Biol. Chem. 284, 4846-4856 (2009).
63. Machner, M. P. & Isberg, R. R. Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev. Cell 11, 47-56 (2006).
64. Jank, T. et al. Domain organization of Legionella effector SetA. Cell. Microbiol. 14, 852-868 (2012).
65. Stebbins, C. E. & Galán, J. E. Structural mimicry in bacterial virulence. Nature 412, 701-705 (2001).
66. Rabin, S. D., Veesenmeyer, J. L, Bieging, K. T. & Hauser, A. R. A. C-terminal domain targets the Pseudomonas aeruginosa cytotoxin ExoU to the plasma membrane of host cells. Infect. Immun. 74, 2552-2561 (2006).
67. Gendrin, C. et al. Structural basis of cytotoxicity mediated by the type III secretion toxin ExoU from Pseudomonas aeruginosa. PLoS Pathog. 8, e1002637 (2012).
68. Finck-Barbancon, V. et al. ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol. Microbiol. 25, 547-557 (1997).
69. Allewelt, M., Coleman, F. T., Grout, M., Priebe, G. P. & Pier, G. B. Acquisition of expression of the Pseudomonas aeruginosa ExoU cytotoxin leads to increased bacterial virulence in a murine model of acute pneumonia and systemic spread. Infect. Immun. 68, 3998-4004 (2000).
70. Marshall, B. & Windsor, H. The relation of Helicobacter pylori to gastric adenocarcinoma and lymphoma: pathophysiology, epidemiology, screening, clinical presentation, treatment, and prevention. Med. Clin. North Am. 89, 313-344 (2005).
71. Murata-Kamiya, N. Pathophysiological functions of the CagA oncoprotein during infection by Helicobacter pylori. Microbes Infect. 13, 799-807 (2011).
72. Murata-Kamiya, N., Kikuchi, K., Hayashi, T., Higashi, H. & Hatakeyama, M. Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. Cell Host Microbe. 7, 399-411 (2010).
73. Higashi, H. et al. EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. J. Biol. Chem. 280, 23130-23137 (2005).
74. Neupert, W Protein import into mitochondria. Annu. Rev. Biochem. 66, 863-917 (1997).
75. Schatz, G. The protein import system of mitochondria. J. Biol. Chem. 271, 31763-31766 (1996).
76. Wiedemann, N., Frazier, A. E. & Pfanner, N. The protein import machinery of mitochondria. J. Biol. Chem. 279, 14473-14476 (2004).
77. Guttman, D. S. et al. A functional screen for the type III (Hrp) secretome of the plant pathogen Pseudomonas syringae. Science 295, 1722-1726 (2002).
78. Jelenska, J. et al. A J domain virulence effector of Pseudomonas syringae remodels host chloroplasts and suppresses defenses. Curr. Biol. 17, 499-508 (2007).
79. Block, A. et al. The Pseudomonas syringae type III effector HopG1 targets mitochondria, alters plant development and suppresses plant innate immunity. Cell. Microbiol. 12, 318-330 (2010).
80. Kenny, B. & Jepson, M. Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria. Cell. Microbiol. 2, 579-590 (2000).
81. Nougayrede, J. P. & Donnenberg, M. S. Enteropathogenic Escherichia coli EspF is targeted to mitochondria and is required to initiate the mitochondrial death pathway. Cell. Microbiol. 6, 1097-1111 (2004).
82. Papatheodorou, P. et al. The enteropathogenic Escherichia coli (EPEC) Map effector is imported into the mitochondrial matrix by the TOM/Hsp70 system and alters organelle morphology. Cell. Microbiol. 8, 677-689 (2006).
83. Alto, N. M. et al. Identification of a bacterial type III effector family with G protein mimicry functions. Cell 124, 133-145 (2006).
84. Bulgin, R. et al. Bacterial guanine nucleotide exchange factors SopE-like and WxxxE effectors. Infect. Immun. 78, 1417-1425 (2010).
85. Hodges, K., Alto, N. M., Ramaswamy, K., Dudeja, P. K. & Hecht, G. The enteropathogenic Escherichia coli effector protein EspF decreases sodium hydrogen exchanger 3 activity. Cell. Microbiol. 10, 1735-1745 (2008).
86. Simpson, N. et al. The enteropathogenic Escherichia coli type III secretion system effector Map binds EBP50/NHERF1: implication for cell signalling and diarrhoea. Mol. Microbiol. 60, 349-363 (2006).
87. Alto, N. M. et al. The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways. J. Cell Biol. 178, 1265-1278 (2007).
88. Dean, P. et al. The enteropathogenic E. coli effector EspF targets and disrupts the nucleolus by a process regulated by mitochondrial dysfunction. PLoS Pathog. 6, e1000961 (2010).
89. Marches, O. et al. EspF of enteropathogenic Escherichia coli binds sorting nexin 9. J. Bacteriol. 188, 3110-3115 (2006).
90. Wong, A. R. et al. Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements. Mol. Microbiol. 80, 1420-1438 (2011).
91. Holmes, A., Muhlen, S., Roe, A. J. & Dean, P. The EspF effector, a bacterial pathogen's Swiss army knife. Infect. Immun. 78, 4445-4453 (2010).
92. Pistor, S., Chakraborty, T., Niebuhr, K., Domann, E. & Wehland, J. The ActA protein of Listeria monocytogenes acts as a nucleator inducing reorganization of the actin cytoskeleton. EMBO J. 13, 758-763 (1994).
93. Zurawski, D., Mumy, K., Faherty, C., McCormick, B. & Maurelli, A. Shigella flexneri T3SS effectors OspB and OspF target the nucleus to down-regulate the host inflammatory response via interactions with retinoblastoma protein. Mol. Microbiol. 71, 350-368 (2009).
94. Bogdanove, A. J., Schornack, S. & Lahaye, T. TAL effectors: finding plant genes for disease and defense. Curr. Opin. Plant Biol. 13, 394-401 (2010).
95. Boch, J. & Bonas, U. Xanthomonas AvrBs3 family-type III effectors: discovery and function. Annu. Rev. Phytopathol. 48, 419-436 (2010).
96. Howard, E. A., Zupan, J. R., Citovsky, V. & Zambryski, P. C. The VirD2 protein of A. tumefaciens contains a C-terminal bipartite nuclear localization signal: implications for nuclear uptake of DNA in plant cells. Cell 68, 109-118 (1992).
97. Rossi, L., Hohn, B. & Tinland, B. The VirD2 protein of Agrobacterium tumefaciens carries nuclear localization signals important for transfer of T-DNA to plant. Mol. Gen. Genet. 239, 345-353 (1993).
98. Gelvin, S. Finding a way to the nucleus. Curr. Opin. Microbiol. 13, 53-58 (2010).
99. Daniel, V. et al. Shigella flexneri T3SS effectors OspB and OspF target the nucleus to down-regulate the host inflammatory response via interactions with retinoblastoma protein. Mol. Microbiol. 71, 350-368 (2009).
100. Haraga, A. & Miller, S. I. A. Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1. Cell. Microbiol. 8, 837-846 (2006).
101. Mattaj, I. W. & Englmeier, L. Nucleocytoplasmic transport: the soluble phase. Annu. Rev. Biochem. 67, 265-306 (1998).
102. Gorlich, D. et al. Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope. Curr. Biol. 5, 383-392 (1995).
103. Gorlich, D., Prehn, S., Laskey, R. A. & Hartmann, E. Isolation of a protein that is essential for the first step of nuclear protein import. Cell 79, 767-778 (1994).
104. Gorlich, D., Vogel, F., Mills, A. D., Hartmann, E. & Laskey, R. A. Distinct functions for the two importin subunits in nuclear protein import. Nature 377, 246-248 (1995).
105. Lee, S. J., Matsuura, Y., Liu, S. M. & Stewart, M. Structural basis for nuclear import complex dissociation by RanGTP. Nature 435, 693-696 (2005).
106. Marois, E., Van den Ackerveken, G. & Bonas, U. The Xanthomonas type III effector protein AvrBs3 modulates plant gene expression and induces cell hypertrophy in the susceptible host. Mol. Plant Microbe Interact. 15, 637-646 (2002).
107. Van den Ackerveken, G., Marois, E. & Bonas, U. Recognition of the bacterial avirulence protein AvrBs3 occurs inside the host plant cell. Cell 87, 1307-1316 (1996).
108. Lahaye, T. & Bonas, U. Molecular secrets of bacterial type III effector proteins. Trends Plant Sci. 6, 479-485 (2001).
109. Yang, Y. & Gabriel, D. W. Xanthomonas avirulence/pathogenicity gene family encodes functional plant nuclear targeting signals. Mol. Plant Microbe Interact. 8, 627-631 (1995).
110. Szurek, B., Marois, E., Bonas, U. & Van den Ackerveken, G. Eukaryotic features of the Xanthomonas type III effector AvrBs3: protein domains involved in transcriptional activation and the interaction with nuclear import receptors from pepper. Plant J. 26, 523-534 (2001).
111. Pitzschke, A. & Hirt, H. New insights into an old story: Agrobacterium-induced tumour formation in plants by plant transformation. EMBO J. 29, 1021-1032 (2010).
112. Citovsky, V., Zupan, J., Warnick, D. & Zambryski, P. Nuclear localization of Agrobacterium VirE2 protein in plant cells. Science 256, 1802-1805 (1992).
113. Zupan, J. R., Citovsky, V. & Zambryski, P. Agrobacterium VirE2 protein mediates nuclear uptake of single-stranded DNA in plant cells. Proc. Natl Acad. Sci. USA 93, 2392-2397 (1996).
114. Ballas, N. & Citovsky, V. Nuclear localization signal binding protein from Arabidopsis mediates nuclear import of Agrobacterium VirD2 protein. Proc. Natl Acad. Sci. USA 94, 10723-10728 (1997).
115. Citovsky, V., Warnick, D. & Zambryski, P. Nuclear import of Agrobacterium VirD2 and VirE2 proteins in maize and tobacco. Proc. Natl Acad. Sci. USA 91, 3210-3214 (1994).
116. Nagai, T., Abe, A. & Sasakawa, C. Targeting of enteropathogenic Escherichia coli EspF to host mitochondria is essential for bacterial pathogenesis: critical role of the 16th leucine residue in EspF. J. Biol. Chem. 280, 2998-3011 (2005).
117. Hartland, E. L. et al. Binding of intimin from enteropathogenic Escherichia coli to Tir and to host cells. Mol. Microbiol. 32, 151-158 (1999).
118. Liu, H. et al. Point mutants of EHEC intimin that diminish Tir recognition and actin pedestal formation highlight a putative Tir binding pocket. Mol. Microbiol. 45, 1557-1573 (2002).
119. Luo, Y. et al. Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature 405, 1073-1077 (2000).
120. Murata, T. et al. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nature Cell Biol. 8, 971-977 (2006).
121. de Vries, J. S., Andriotis, V. M. E., Wu, A.-J. & Rathjen, J. P. Tomato Pto encodes a functional N-myristoylation motif that is required for signal transduction in Nicotiana benthamiana. Plant J. 45, 31-45 (2006).
122. Hernandez, L. D., Pypaert, M., Flavell, R. A. & Galán, J. E. A. Salmonella protein causes macrophage cell death by inducing autophagy. J. Cell Biol. 163, 1123-1131 (2003).
123. Layton, A. N., Brown, P. J. & Galyov, E. E. The Salmonella translocated effector SopA is targeted to the mitochondria of infected cells. J. Bacteriol. 187, 3565-3571 (2005).
124. Zou, H. et al. Identification of an avirulence gene, avrxa5, from the rice pathogen Xanthomonas oryzae pv. oryzae. Sci. China Life Sci. 53, 1440-1449 (2010).
125. Yang, B., Zhu, W., Johnson, L. B. & White, F. F. The virulence factor AvrXa7 of Xanthomonas oryzae p v. oryzae is a type III secretion pathway-dependent nuclear-localized double-stranded DNA-binding protein. Proc. Natl Acad. Sci. USA 97, 9807-9812 (2000).