Biochemical functions of Yersinia type III effectors

Current Opinion in Microbiology

Volumn 11, Issue 1, 2008, Pages 21-29

  Shao, Feng ^a  

^a NATIONAL INSTITUTE OF BIOLOGICAL SCIENCES   (China)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; CYSTEINE PROTEINASE; CYTOKINE; GUANINE NUCLEOTIDE BINDING PROTEIN; I KAPPA B KINASE; LEUCINE RICH REPEAT KINASE 2; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PHOSPHOTRANSFERASE; PROTEIN; PROTEIN TYROSINE PHOSPHATASE; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; SERINE; THREONINE; UNCLASSIFIED DRUG; YERSINIA OUTER PROTEIN E; YERSINIA OUTER PROTEIN H; YERSINIA OUTER PROTEIN T; YOPM PROTEIN;

ACETYLATION; ADAPTIVE IMMUNITY; APOPTOSIS; BIOCHEMISTRY; CYTOKINE PRODUCTION; CYTOSKELETON; DEPHOSPHORYLATION; ENZYME METABOLISM; ENZYME PHOSPHORYLATION; FOCAL ADHESION; HOST CELL; IMMUNE RESPONSE; IMMUNITY; INFECTION; INNATE IMMUNITY; MOLECULAR MIMICRY; NONHUMAN; PHAGOCYTE; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; YERSINIA;

BACTERIAL PROTEINS; HUMANS; SIGNAL TRANSDUCTION; VIRULENCE FACTORS; YERSINIA; YERSINIA INFECTIONS;

YERSINIA;

EID: 40849116186     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mib.2008.01.005     Document Type: Review

References (50)

1. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 449 (2007) 819-826
2. Bhavsar A.P., Guttman J.A., and Finlay B.B. Manipulation of host-cell pathways by bacterial pathogens. Nature 449 (2007) 827-834
3. Viboud G.I., and Bliska J.B. Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol 59 (2005) 69-89
4. Matsumoto H., and Young G.M. Proteomic and functional analysis of the suite of Ysp proteins exported by the Ysa type III secretion system of Yersinia enterocolitica Biovar 1B. Mol Microbiol 59 (2006) 689-706
5. Ivanov M.I., Stuckey J.A., Schubert H.L., Saper M.A., and Bliska J.B. Two substrate-targeting sites in the Yersinia protein tyrosine phosphatase co-operate to promote bacterial virulence. Mol Microbiol 55 (2005) 1346-1356
6. Bruce-Staskal P.J., Weidow C.L., Gibson J.J., and Bouton A.H. Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake. J Cell Sci 115 (2002) 2689-2700
7. Deleuil F., Mogemark L., Francis M.S., Wolf-Watz H., and Fallman M. Interaction between the Yersinia protein tyrosine phosphatase YopH and eukaryotic Cas/Fyb is an important virulence mechanism. Cell Microbiol 5 (2003) 53-64
8. Sauvonnet N., Lambermont I., van der Bruggen P., and Cornelis G.R. YopH prevents monocyte chemoattractant protein 1 expression in macrophages and T-cell proliferation through inactivation of the phosphatidylinositol 3-kinase pathway. Mol Microbiol 45 (2002) 805-815
9. Alonso A., Bottini N., Bruckner S., Rahmouni S., Williams S., Schoenberger S.P., and Mustelin T. Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH. J Biol Chem 279 (2004) 4922-4928
10. Gerke C., Falkow S., and Chien Y.H. The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. J Exp Med 201 (2005) 361-371
11. Prehna G., Ivanov M.I., Bliska J.B., and Stebbins C.E. Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors. Cell 126 (2006) 869-880. Through structural and biochemical analysis, the authors found that the C-terminus of YpkA binds to RhoA/Rac1 in a manner similar to RhoGDI, which inhibits their nucleotide exchange activity. This observation provides a mechanistic understanding for the previously observed kinase-independent function of YpkA in Yersinia pathogenesis.
12. Wiley D.J., Nordfeldth R., Rosenzweig J., DaFonseca C.J., Gustin R., Wolf-Watz H., and Schesser K. The Ser/Thr kinase activity of the Yersinia protein kinase A (YpkA) is necessary for full virulence in the mouse, mollifying phagocytes, and disrupting the eukaryotic cytoskeleton. Microb Pathog 40 (2006) 234-243
13. Navarro L., Koller A., Nordfelth R., Wolf-Watz H., Taylor S., and Dixon J.E. Identification of a molecular target for the Yersinia protein kinase A. Mol Cell 26 (2007) 465-477. The authors demonstrated that YpkA could phosphorylate trimeric G protein in vitro and in cultured cells, providing the first and a strong candidate for the long-sought kinase substrate for YpkA. This study also brings in the idea whether trimeric G protein signaling plays a role in counteracting pathogen invasion.
14. Trasak C., Zenner G., Vogel A., Yuksekdag G., Rost R., Haase I., Fischer M., Israel L., Imhof A., Linder S., et al. Yersinia protein kinase YopO is activated by a novel G-actin binding process. J Biol Chem 282 (2007) 2268-2277
15. Park H., Teja K., O'Shea J.J., and Siegel R.M. The Yersinia effector protein YpkA induces apoptosis independently of actin depolymerization. J Immunol 178 (2007) 6426-6434. These authors for the first time show that YpkA has functions other than modulation of cytoskeleton structure. This seems to fit better with its kinase function and phosphorylation of Gα.
16. Aili M., Isaksson E.L., Hallberg B., Wolf-Watz H., and Rosqvist R. Functional analysis of the YopE GTPase-activating protein (GAP) activity of Yersinia pseudotuberculosis. Cell Microbiol 8 (2006) 1020-1033
17. Krall R., Zhang Y., and Barbieri J.T. Intracellular membrane localization of pseudomonas ExoS and Yersinia YopE in mammalian cells. J Biol Chem 279 (2004) 2747-2753
18. Schotte P., Denecker G., Van Den Broeke A., Vandenabeele P., Cornelis G.R., and Beyaert R. Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta. J Biol Chem 279 (2004) 25134-25142
19. Wong K.W., and Isberg R.R. Yersinia pseudotuberculosis spatially controls activation and misregulation of host cell Rac1. PLoS Pathog 1 (2005) e16
20. Hentschke M., Trulzsch K., Heesemann J., Aepfelbacher M., and Ruckdeschel K. Serogroup-related escape of Yersinia enterocolitica YopE from degradation by the ubiquitin-proteasome pathway. Infect Immun 75 (2007) 4423-4431
21. Ruckdeschel K., Pfaffinger G., Trulzsch K., Zenner G., Richter K., Heesemann J., and Aepfelbacher M. The proteasome pathway destabilizes Yersinia outer protein E and represses its antihost cell activities. J Immunol 176 (2006) 6093-6102. These two interesting studies show that YopE is ubiquitinated and degraded in the host cell, and ubiquitination appears to negatively correlate with virulence. Ubiquitination in bacteria-host interaction is an emerging new concept.
22. Shao F., Merritt P.M., Bao Z., Innes R.W., and Dixon J.E. A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell 109 (2002) 575-588
23. Sorg I., Hoffmann C., Dumbach J., Aktories K., and Schmidt G. The C terminus of YopT is crucial for activity and the N terminus is crucial for substrate binding. Infect Immun 71 (2003) 4623-4632
24. Shao F., Vacratsis P.O., Bao Z., Bowers K.E., Fierke C.A., and Dixon J.E. Biochemical characterization of the Yersinia YopT protease: cleavage site and recognition elements in Rho GTPases. Proc Natl Acad Sci U S A 100 (2003) 904-909
25. Aepfelbacher M., Trasak C., Wilharm G., Wiedemann A., Trulzsch K., Krauss K., Gierschik P., and Heesemann J. Characterization of YopT effects on Rho GTPases in Yersinia enterocolitica-infected cells. J Biol Chem 278 (2003) 33217-33223
26. Viboud G.I., Mejia E., and Bliska J.B. Comparison of YopE and YopT activities in counteracting host signalling responses to Yersinia pseudotuberculosis infection. Cell Microbiol 8 (2006) 1504-1515. Both YopT and YopE target Rho GTPases and inactivate them, and functions of these two effectors were thought to be redundant. The authors took genetic approaches and carried out a rather comprehensive study to compare the effect of YopT and YopE at many aspects of Yersinia pathogenesis, including virulence, antiphagocytosis, cytokine induction, and pore formation.
27. Zhu M., Shao F., Innes R.W., Dixon J.E., and Xu Z. The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site. Proc Natl Acad Sci U S A 101 (2004) 302-307
28. Orth K. Function of the Yersinia effector YopJ. Curr Opin Microbiol 5 (2002) 38-43
29. Zhou H., Monack D.M., Kayagaki N., Wertz I., Yin J., Wolf B., and Dixit V.M. Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-kappa B activation. J Exp Med 202 (2005) 1327-1332
30. Carter R.S., Pennington K.N., Ungurait B.J., Arrate P., and Ballard D.W. Signal-induced ubiquitination of I kappaB Kinase-beta. J Biol Chem 278 (2003) 48903-48906
31. Haase R., Richter K., Pfaffinger G., Courtois G., and Ruckdeschel K. Yersinia outer protein P suppresses TGF-beta-activated kinase-1 activity to impair innate immune signaling in Yersinia enterocolitica-infected cells. J Immunol 175 (2005) 8209-8217
32. Thiefes A., Wolf A., Doerrie A., Grassl G.A., Matsumoto K., Autenrieth I., Bohn E., Sakurai H., Niedenthal R., Resch K., et al. The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway. EMBO Rep 7 (2006) 838-844
33. Sweet C.R., Conlon J., Golenbock D.T., Goguen J., and Silverman N. YopJ targets TRAF proteins to inhibit TLR-mediated NF-kappaB, MAPK and IRF3 signal transduction. Cell Microbiol 9 (2007) 2700-2715
34. Mittal R., Peak-Chew S.Y., and McMahon H.T. Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signalling. Proc Natl Acad Sci U S A 103 (2006) 18574-18579
35. Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., and Orth K. Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation. Science 312 (2006) 1211-1214. These two studies provide direct and convincing biochemical evidences that YopJ functions as an acetyltransferase to modify serine and threonine residues in the activation loop of both MKKs and IKKs, which prevents their activation by phosphorylation. This observation solves the long-standing mystery how YopJ simultaneously blocks multiple signaling pathways.
36. Mukherjee S., Hao Y.H., and Orth K. A newly discovered post-translational modification-the acetylation of serine and threonine residues. Trends Biochem Sci 32 (2007) 210-216. This review presents in-depth analysis of the newly discovered Ser/Thr acetyltransferase activity of the YopJ family of effectors including potential catalytic mechanism and its implications for mammalian signal transduction system.
37. Trosky J.E., Li Y., Mukherjee S., Keitany G., Ball H., and Orth K. VopA inhibits ATP binding by acetylating the catalytic loop of MAPK kinases. J Biol Chem 282 (2007) 34299-34305
38. Zhang Y., Ting A.T., Marcu K.B., and Bliska J.B. Inhibition of MAPK and NF-kappa B pathways is necessary for rapid apoptosis in macrophages infected with Yersinia. J Immunol 174 (2005) 7939-7949
39. Zhang Y., and Bliska J.B. Role of Toll-like receptor signaling in the apoptotic response of macrophages to Yersinia infection. Infect Immun 71 (2003) 1513-1519
40. Denecker G., Declercq W., Geuijen C.A., Boland A., Benabdillah R., van Gurp M., Sory M.P., Vandenabeele P., and Cornelis G.R. Yersinia enterocolitica YopP-induced apoptosis of macrophages involves the apoptotic signaling cascade upstream of bid. J Biol Chem 276 (2001) 19706-19714
41. Autenrieth S.E., Soldanova I., Rosemann R., Gunst D., Zahir N., Kracht M., Ruckdeschel K., Wagner H., Borgmann S., and Autenrieth I.B. Yersinia enterocolitica YopP inhibits MAP kinase-mediated antigen uptake in dendritic cells. Cell Microbiol 9 (2007) 425-437. This study, for the first time, shows that YopJ inhibits antigen uptake, one important function of dendritic cells. This new function of YopJ also requires the catalytic residues and its inhibitory effect over MAPK signaling.
42. Lindner I., Torruellas-Garcia J., Kolonias D., Carlson L.M., Tolba K.A., Plano G.V., and Lee K.P. Modulation of dendritic cell differentiation and function by YopJ of Yersinia pestis. Eur J Immunol 37 (2007) 2450-2462
43. Hines J., Skrzypek E., Kajava A.V., and Straley S.C. Structure-function analysis of Yersinia pestis YopM's interaction with alpha-thrombin to rule on its significance in systemic plague and to model YopM's mechanism of binding host proteins. Microb Pathog 30 (2001) 193-209
44. Kerschen E.J., Cohen D.A., Kaplan A.M., and Straley S.C. The plague virulence protein YopM targets the innate immune response by causing a global depletion of NK cells. Infect Immun 72 (2004) 4589-4602
45. Benabdillah R., Mota L.J., Lutzelschwab S., Demoinet E., and Cornelis G.R. Identification of a nuclear targeting signal in YopM from Yersinia spp. Microb Pathog 36 (2004) 247-261
46. Skrzypek E., Myers-Morales T., Whiteheart S.W., and Straley S.C. Application of a Saccharomyces cerevisiae model to study requirements for trafficking of Yersinia pestis YopM in eucaryotic cells. Infect Immun 71 (2003) 937-947
47. Evdokimov A.G., Anderson D.E., Routzahn K.M., and Waugh D.S. Unusual molecular architecture of the Yersinia pestis cytotoxin YopM: a leucine-rich repeat protein with the shortest repeating unit. J Mol Biol 312 (2001) 807-821
48. McDonald C., Vacratsis P.O., Bliska J.B., and Dixon J.E. The Yersinia virulence factor YopM forms a novel protein complex with two cellular kinases. J Biol Chem 278 (2003) 18514-18523
49. Haraga A., and Miller S.I. A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1. Cell Microbiol 8 (2006) 837-846
50. Rohde J.R., Breitkreutz A., Chenal A., Sansonetti P.J., and Parsot C. Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe 1 (2007) 77-83. In this elegant study, the LRR-containing TTSS effectors from Shigella and Salmonella (IpaHs and SspH1) were demonstrated to have a robust in vitro E3 ligase activity of catalyzing ubiquitin chain formation from monomeric ubiquitin.