Tertiary Structure-Function Analysis Reveals the Pathogenic Signaling Potentiation Mechanism of Helicobacter pylori Oncogenic Effector CagA

Cell Host and Microbe

Volumn 12, Issue 1, 2012, Pages 20-33

  Hayashi, Takeru ^a,b   Senda, Miki ^c   Morohashi, Hiroko ^a   Higashi, Hideaki ^b   Horio, Masafumi ^b   Kashiba, Yui ^a   Nagase, Lisa ^a   Sasaya, Daisuke ^b   Shimizu, Tomohiro ^b   Venugopalan, Nagarajan ^d   Kumeta, Hiroyuki ^b   Noda, Nobuo N ^e   Inagaki, Fuyuhiko ^b   Senda, Toshiya ^f   Hatakeyama, Masanori ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b HOKKAIDO UNIVERSITY   (Japan)

^c Koto ku   (Japan)

^d ARGONNE NATIONAL LABORATORY   (United States)

^e INSTITUTE OF MICROBIAL CHEMISTRY   (Japan)

^f NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY AIST   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; BACTERIAL PROTEIN; CAGA PROTEIN; MEMBRANE PHOSPHOLIPID; ONCOPROTEIN; PHOSPHATIDYLSERINE; RECOMBINANT PROTEIN; BACTERIAL ANTIGEN; CAGA PROTEIN, HELICOBACTER PYLORI; PROTEINASE ACTIVATED RECEPTOR 1;

ARTICLE; BACTERIAL VIRULENCE; CELL MEMBRANE; CRYSTAL STRUCTURE; HELICOBACTER PYLORI; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; STOMACH CARCINOGENESIS; STRUCTURE ACTIVITY RELATION; TYPE IV SECRETION SYSTEM; X RAY CRYSTALLOGRAPHY; AMINO ACID SEQUENCE; CHEMISTRY; GENETICS; METABOLISM; MOLECULAR GENETICS; NUCLEAR MAGNETIC RESONANCE; PATHOGENICITY; PROTEIN TERTIARY STRUCTURE; SIGNAL TRANSDUCTION; SURFACE PLASMON RESONANCE;

AMINO ACID SEQUENCE; ANTIGENS, BACTERIAL; BACTERIAL PROTEINS; CELL MEMBRANE; CRYSTALLOGRAPHY, X-RAY; HELICOBACTER PYLORI; MOLECULAR SEQUENCE DATA; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PROTEIN STRUCTURE, TERTIARY; RECEPTOR, PAR-1; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; SURFACE PLASMON RESONANCE;

EID: 84872005854     PISSN: 19313128     EISSN: 19346069     Source Type: Journal    
DOI: 10.1016/j.chom.2012.05.010     Document Type: Article

References (44)

1. 1 ATPase. Acta Crystallogr. D Biol. Crystallogr. 52 (1996), 30–42.
2. Adams, P.D., Afonine, P.V., Bunkóczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.W., Kapral, G.J., Grosse-Kunstleve, R.W., et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66 (2010), 213–221.
3. Angelini, A., Tosi, T., Mas, P., Acajjaoui, S., Zanotti, G., Terradot, L., Hart, D.J., Expression of Helicobacter pylori CagA domains by library-based construct screening. FEBS J. 276 (2009), 816–824.
4. Backert, S., Meyer, T.F., Type IV secretion systems and their effectors in bacterial pathogenesis. Curr. Opin. Microbiol. 9 (2006), 207–217.
5. Bagnoli, F., Buti, L., Tompkins, L., Covacci, A., Amieva, M.R., Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells. Proc. Natl. Acad. Sci. USA 102 (2005), 16339–16344.
6. Blaser, M.J., Atherton, J.C., Helicobacter pylori persistence: biology and disease. J. Clin. Invest. 113 (2004), 321–333.
7. Buti, L., Spooner, E., Van den Veen, A., Rappuoli, R., Covacci, A., Ploegh, H.L., Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host. Proc. Natl. Acad. Sci. USA 108 (2011), 9238–9243.
8. Covacci, A., Rappuoli, R., Tyrosine-phosphorylated bacterial proteins: Trojan horses for the host cell. J. Exp. Med. 191 (2000), 587–592.
9. Dunker, A.K., Silman, I., Uversky, V.N., Sussman, J.L., Function and structure of inherently disordered proteins. Curr. Opin. Struct. Biol. 18 (2008), 756–764.
10. Dyson, H.J., Wright, P.E., Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 6 (2005), 197–208.
11. Emsley, P., Lohkamp, B., Scott, W.G., Cowtan, K., Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66 (2010), 486–501.
12. Fink, A.L., Natively unfolded proteins. Curr. Opin. Struct. Biol. 15 (2005), 35–41.
13. Hatakeyama, M., Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat. Rev. Cancer 4 (2004), 688–694.
14. Hatakeyama, M., Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA. Oncogene 27 (2008), 7047–7054.
15. Higashi, H., Tsutsumi, R., Fujita, A., Yamazaki, S., Asaka, M., Azuma, T., Hatakeyama, M., Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc. Natl. Acad. Sci. USA 99 (2002), 14428–14433.
16. Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., Hatakeyama, M., SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori Cag. Science 295 (2002), 683–686.
17. Higashi, H., Yokoyama, K., Fujii, Y., Ren, S., Yuasa, H., Saadat, I., Murata-Kamiya, N., Azuma, T., Hatakeyama, M., EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. J. Biol. Chem. 280 (2005), 23130–23137.
18. Hohlfeld, S., Pattis, I., Püls, J., Plano, G.V., Haas, R., Fischer, W., A C-terminal translocation signal is necessary, but not sufficient for type IV secretion of the Helicobacter pylori CagA protein. Mol. Microbiol. 59 (2006), 1624–1637.
19. Holm, L., Sander, C., Mapping the protein universe. Science 273 (1996), 595–603.
20. Jiménez-Soto, L.F., Kutter, S., Sewald, X., Ertl, C., Weiss, E., Kapp, U., Rohde, M., Pirch, T., Jung, K., Retta, S.F., et al. Helicobacter pylori type IV secretion apparatus exploits β1 integrin in a novel RGD-independent manner. PLoS Pathog., 5, 2009, e1000684.
21. Kwok, T., Zabler, D., Urman, S., Rohde, M., Hartig, R., Wessler, S., Misselwitz, R., Berger, J., Sewald, N., König, W., Backert, S., Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449 (2007), 862–866.
22. Lu, H.S., Saito, Y., Umeda, M., Murata-Kamiya, N., Zhang, H.M., Higashi, H., Hatakeyama, M., Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CagA. Cancer Sci. 99 (2008), 2004–2011.
23. Lu, H., Murata-Kamiya, N., Saito, Y., Hatakeyama, M., Role of partitioning-defective 1/microtubule affinity-regulating kinases in the morphogenetic activity of Helicobacter pylori CagA. J. Biol. Chem. 284 (2009), 23024–23036.
24. Mimuro, H., Suzuki, T., Tanaka, J., Asahi, M., Haas, R., Sasakawa, C., Grb2 is a key mediator of helicobacter pylori CagA protein activities. Mol. Cell 10 (2002), 745–755.
25. Moese, S., Selbach, M., Zimny-Arndt, U., Jungblut, P.R., Meyer, T.F., Backert, S., Identification of a tyrosine-phosphorylated 35 kDa carboxy-terminal fragment (p35CagA) of the Helicobacter pylori CagA protein in phagocytic cells: processing or breakage?. Proteomics 1 (2001), 618–629.
26. Mohi, M.G., Neel, B.G., The role of Shp2 (PTPN11) in cancer. Curr. Opin. Genet. Dev. 17 (2007), 23–30.
27. 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 (2010), 399–411.
28. Nagase, L., Murata-Kamiya, N., Hatakeyama, M., Potentiation of Helicobacter pylori CagA protein virulence through homodimerization. J. Biol. Chem. 286 (2011), 33622–33631.
29. Nesić D., Miller, M.C., Quinkert, Z.T., Stein, M., Chait, B.T., Stebbins, C.E., Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates. Nat. Struct. Mol. Biol. 17 (2010), 130–132.
30. Ohnishi, N., Yuasa, H., Tanaka, S., Sawa, H., Miura, M., Matsui, A., Higashi, H., Musashi, M., Iwabuchi, K., Suzuki, M., et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc. Natl. Acad. Sci. USA 105 (2008), 1003–1008.
31. Parsonnet, J., Friedman, G.D., Orentreich, N., Vogelman, H., Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 40 (1997), 297–301.
32. Pelz, C., Steininger, S., Weiss, C., Coscia, F., Vogelmann, R., A novel inhibitory domain of Helicobacter pylori protein CagA reduces CagA effects on host cell biology. J. Biol. Chem. 286 (2011), 8999–9008.
33. Ren, S., Higashi, H., Lu, H., Azuma, T., Hatakeyama, M., Structural basis and functional consequence of Helicobacter pylori CagA multimerization in cells. J. Biol. Chem. 281 (2006), 32344–32352.
34. Rohde, M., Püls, J., Buhrdorf, R., Fischer, W., Haas, R., A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system. Mol. Microbiol. 49 (2003), 219–234.
35. Saadat, I., Higashi, H., Obuse, C., Umeda, M., Murata-Kamiya, N., Saito, Y., Lu, H., Ohnishi, N., Azuma, T., Suzuki, A., et al. Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature 447 (2007), 330–333.
36. Segal, E.D., Cha, J., Lo, J., Falkow, S., Tompkins, L.S., Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc. Natl. Acad. Sci. USA 96 (1999), 14559–14564.
37. Selbach, M., Paul, F.E., Brandt, S., Guye, P., Daumke, O., Backert, S., Dehio, C., Mann, M., Host cell interactome of tyrosine-phosphorylated bacterial proteins. Cell Host Microbe 5 (2009), 397–403.
38. Sigalov, A.B., Protein intrinsic disorder and oligomericity in cell signaling. Mol. Biosyst. 6 (2010), 451–461.
39. Suzuki, M., Mimuro, H., Suzuki, T., Park, M., Yamamoto, T., Sasakawa, C., Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J. Exp. Med. 202 (2005), 1235–1247.
40. Suzuki, M., Mimuro, H., Kiga, K., Fukumatsu, M., Ishijima, N., Morikawa, H., Nagai, S., Koyasu, S., Gilman, R.H., Kersulyte, D., et al. Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell Host Microbe 5 (2009), 23–34.
41. Tsang, Y.H., Lamb, A., Romero-Gallo, J., Huang, B., Ito, K., Peek, R.M. Jr., Ito, Y., Chen, L.F., Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation. Oncogene 29 (2010), 5643–5650.
42. Vonrhein, C., Blanc, E., Roversi, P., Bricogne, G., Automated structure solution with autoSHARP. Methods Mol. Biol. 364 (2007), 215–230.
43. Xia, Y., Yamaoka, Y., Zhu, Q., Matha, I., Gao, X., A comprehensive sequence and disease correlation analyses for the C-terminal region of CagA protein of Helicobacter pylori. PLoS ONE, 4, 2009, e7736.
44. Zeaiter, Z., Cohen, D., Müsch, A., Bagnoli, F., Covacci, A., Stein, M., Analysis of detergent-resistant membranes of Helicobacter pylori infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b in CagA-mediated disruption of cellular polarity. Cell. Microbiol. 10 (2008), 781–794.