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Mapping of the Complement C9 Binding Region on Clonorchis sinensis Paramyosin

  • Kang, Jung-Mi (Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine) ;
  • Le, Huong Giang (Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine) ;
  • Vo, Tuan Cuong (Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine) ;
  • Yoo, Won Gi (Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine) ;
  • Sohn, Woon-Mok (Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine) ;
  • Na, Byoung-Kuk (Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University College of Medicine)
  • Received : 2022.05.29
  • Accepted : 2022.07.07
  • Published : 2022.08.31

Abstract

Heliminthic paramyosin is a multifunctional protein that not only acts as a structural protein in muscle layers but as an immune-modulatory molecule interacting with the host immune system. Previously, we found that paramyosin from Clonorchis sinensis (CsPmy) is bound to human complement C9 protein (C9). To analyze the C9 binding region on CsPmy, overlapping recombinant fragments of CsPmy were produced and their binding activity to human C9 was investigated. The fragmental expression of CsPmy and C9 binding assays revealed that the C9 binding region was located at the C-terminus of CsPmy. Further analysis of the C-terminus of CsPmy to narrow the C9 binding region on CsPmy indicated that the region flanking 731Leu-780Leu was a potent C9 binding region. The CsPmy fragments corresponding to the region effectively inhibited human C9 polymerization. These results provide a precise molecular basis for CsPmy as a potent immunomodulator to evade host immune defenses by inhibiting complement attack.

Keywords

Acknowledgement

This work was supported by a grant from the National Research Foundation (NRF) funded by the Korean government (NRF-2016R1C1B1009348).

References

  1. Choi BI, Han JK, Hong ST, Lee K. Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis. Clin Microbiol Rev 2004; 17: 540-552. http://doi.org/10.1128/CMR.17.3.540-552.2004
  2. Na BK, Pak JH, Hong SJ. Clonorchis sinensis and clonorchiasis. Acta Trop 2020; 203: 105309. http://doi.org/10.1016/j.actatropica.2019.105309
  3. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V. A review of human carcinogens-Part B: biological agents. Lancet Oncol 2009; 10: 321-322. http://doi.org/10.1016/s1470-2045(09)70096-8
  4. Cohen C, Szent-Gyorgyi AG, Kendrick-Jones J. Paramyosin and the filaments of molluscan "catch" muscles. I. Paramyosin: structure and assembly. J Mol Biol 1971; 56: 223-227. http://doi.org/10.1016/0022-2836(71)90461-x
  5. Elfvin M, Levine RJ, Dewey MM. Paramyosin in invertebrate muscles. I. Identification and localization. J Cell Biol 1976; 71: 261-272. http://doi.org/10.1083/jcb.71.1.261
  6. Lanar DE, Pearce EJ, James SL, Sher A. Identification of paramyosin as schistosome antigen recognized by intradermally vaccinated mice. Science 1986; 234: 593-596. http://doi.org/10.1083/jcb.71.1.261
  7. Nanduri J, Kazura JW. Paramyosin-enhanced clearance of Brugia malayi microfilaremia in mice. J Immunol 1989; 43: 3359-3363. https://doi.org/10.4049/jimmunol.143.10.3359
  8. Muhlschlegel F, Sygulla L, Frosch P, Massetti P, Frosch M. Paramyosin of Echinococcus granulosus: cDNA sequence and characterization of a tegumental antigen. Parasitol Res 1993; 79: 660-666. http://doi.org/10.1007/BF00932508
  9. Ferrer E, Moyano E, Benitez L, Gonzalez LM, Bryce D, Foster-Cuevas M, Davila I, Cortez MM, Harrison LJ, Parkhouse RM, Garate T. Cloning and characterization of Taenia saginata paramyosin cDNA. Parasitol Res 2003; 91: 60-67. http://doi.org/10.1007/s00436-003-0895-5
  10. Yang J, Yang Y, Gu Y, Li Q, Wei J, Wang S, Boireau P, Zhu X. Identification and characterization of a full-length cDNA encoding paramyosin of Trichinella spiralis. Biochem Biophys Res Commun 2008; 365: 528-533. http://doi.org/10.1016/j.bbrc.2007.11.012
  11. Cancela M, Carmona C, Rossi S, Frangione B, Goni F, Berasain P. Purification, characterization, and immunolocalization of paramyosin from the adult stage of Fasciola hepatica. Parasitol Res 2004; 92: 441-448. http://doi.org/10.1007/s00436-003-1059-3
  12. Zhao QP, Moon SU, Na BK, Kim SH, Cho SH, Lee HW, Kong Y, Sohn WM, Jiang MS, Kim TS. Paragonimus westermani: biochemical and immunological characterizations of paramyosin. Exp Parasitol 2007; 115: 9-18. http://doi.org/10.1016/j.exppara.2006.05.004
  13. Park TJ, Kang JM, Na BK, Sohn WM. Molecular cloning and characterization of a paramyosin from Clonorchis sinensis. Korean J Parasitol 2009; 47: 359-367. http://doi.org/10.3347/kjp.2009.47.4.359
  14. Laclette JP, Shoemaker CB, Richter D, Arcos L, Pante N, Cohen C, Bing D, Nicholson-Weller A. Paramyosin inhibits complement C1. J Immunol 1992; 148: 124-128. https://doi.org/10.4049/jimmunol.148.1.124
  15. Deng J, Gold D, LoVerde PT, Fishelson Z. Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin. Infect Immun 2003; 71: 6402-6410. https://doi.org/10.1128/IAI.71.11.6402-6410.2003
  16. Zhang Z, Yang J, Wei J, Yang Y, Chen X, Zhao X, Gu Y, Cui S, Zhu X. Trichinella spiralis paramyosin binds to C8 and C9 and protects the tissue-dwelling nematode from being attacked by host complement. PLoS Negl Trop Dis 2011; 5: e1225. http://doi.org/10.1371/journal.pntd.0001225
  17. Loukas A, Jones MK, King LT, Brindley PJ, McManus DP. Receptor for Fc on the surface of schistosomes. Infect Immun 2001; 69: 3646-3651. http://doi.org/10.1128/IAI.69.6.3646-3651.2001
  18. Kalinna B, McManus DP. An IgG (Fc gamma)-binding protein of Taenia crassiceps (Cestoda) exhibits sequence homology and antigenic similarity with schistosome paramyosin. Parasitology 1993; 106: 289-296. http://doi.org/10.1017/s0031182000075119
  19. Kang JM, Ju HL, Lee J, Kim TI, Cho SH, Kim TS, Sohn WM, Na BK. Mapping of the putative epitope domain of Clonorchis sinensis paramyosin (CsPmy) recognized by CsPmy-specific immunoglobulin G in sera of human clonorchiasis. Mol Biochem Parasitol 2015; 201: 66-71. https://doi.org/10.1016/j.molbiopara.2015.06.004
  20. Tschopp J. Circular polymerization of the membranolytic ninth component of complement. Dependence on metal ions. J Biol Chem 1984; 259: 10569-10573. https://doi.org/10.1016/S0021-9258(18)91000-8
  21. Podack ER, Tschopp J. Circular polymerization of the ninth component of complement. Ring closure of the tubular complex confers resistance to detergent dissociation and to proteolytic degradation. J Biol Chem 1982; 257: 15204-15212. https://doi.org/10.1016/S0021-9258(18)33414-8
  22. Jokiranta TS, Jokipii L, Meri S. Complement resistance of parasites. Scand J Immunol 1995; 42: 9-20. http://doi.org/10.1111/j.1365-3083.1995.tb03620.x
  23. Dunkelberger JR, Song WC. Complement and its role in innate and adaptive immune responses. Cell Res 2010; 20: 34-50. http://doi.org/10.1038/cr.2009.139
  24. Fishelson Z. Complement evasion by parasites: search for "Achilles' heel". Clin Exp Immunol 1991; 86 (suppl): 47-52. https://doi.org/10.1111/j.1365-2249.1991.tb06207.x
  25. Lambris JD, Ricklin D, Geisbrecht BV. Complement evasion by human pathogens. Nat Rev Microbiol 2008; 6: 132-142. http://doi.org/10.1038/nrmicro1824
  26. Shao S, Sun X, Chen Y, Zhan B, Zhu X. Complement evasion: an effective strategy that parasites utilize to survive in the host. Front Microbiol 2019; 10: 532. http://doi.org/10.3389/fmicb.2019.00532
  27. Deng J, Gold D, LoVerde PT, Fishelson Z. Mapping of the complement C9 binding domain in paramyosin of the blood fluke Schistosoma mansoni. Int J Parasitol 2007; 37: 67-75. http://doi.org/10.1016/j.ijpara.2006.09.011
  28. Zhao X, Hao Y, Yang J, Gu Y, Zhu X. Mapping of the complement C9 binding domain on Trichinella spiralis paramyosin. Parasit Vectors 2014; 7: 80. http://doi.org/10.1186/1756-3305-7-80