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Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar

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Abstract

Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar (Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

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References

  1. Vyas JM, Van der Veen AG, Ploegh HL (2008) Nat Rev Immunol 8:607–618

    Article  CAS  Google Scholar 

  2. Ruppert J, Sidney J, Celis E, Kubo RT, Grey HM, Sette A (1993) Cell 74:929–937

    Article  CAS  Google Scholar 

  3. NCBI (http://www.ncbi.nlm.nih.gov/gv/mhc/), Inc., 2009

  4. Ellis SA, Bontrop RE, Antczak DF, Ballingall K, Davies CJ, Kaufman J, Kennedy LJ, Robinson J, Smith DM, Stear MJ, Stet RJ, Waller MJ, Walter L, Marsh SG (2006) Immunogenetics 57:953–958

    Article  Google Scholar 

  5. Robinson J, Waller MJ, Fail SC, McWilliam H, Lopez R, Parham P, Marsh SG (2009) Nucleic Acids Res 37:D1013–D1017

    Article  CAS  Google Scholar 

  6. Peters B, Bui H-H, Frankild S, Nielsen M, Lundegaard C, Kostem E, Basch D, Lamberth K, Harndahl M, Fleri W, Wilson SS, Sidney J, Lund O, Buus S, Sette A (2006) PLOS Comput Biol 2:574–584

    Article  CAS  Google Scholar 

  7. Hoof I, Peters B, Sidney J, Pedersen LE, Sette A, Lund O, Buus S, Nielsen M (2009) Immunogenetics 61:1–13

    Article  CAS  Google Scholar 

  8. Rapin N, Hoof I, Lund O, Nielsen M (2008) Immunogenetics 60:759–765

    Article  CAS  Google Scholar 

  9. Reche PA, Glutting JP, Reinherz EL (2002) Hum Immunol 63:701–709

    Article  CAS  Google Scholar 

  10. Tsurui H, Takahashi T (2007) J Pharmacol Sci 105:299–316

    Article  CAS  Google Scholar 

  11. Nielsen M, Lundegaard C, Lund O (2007) BMC Bioinformatics 8:238

    Article  Google Scholar 

  12. Singh H, Raghava GP (2001) Bioinformatics 17:1236–1237

    Article  CAS  Google Scholar 

  13. Lundegaard C, Lamberth K, Harndahl M, Buus S, Lund O, Nielsen M (2008) Nucleic Acids Res 36:W509–W512

    Article  CAS  Google Scholar 

  14. Tenzer S, Peters B, Bulik S, Schoor O, Lemmel C, Schatz MM, Kloetzel PM, Rammensee HG, Schild H, Holzhutter HG (2005) Cell Mol Life Sci 62:1025–1037

    Article  CAS  Google Scholar 

  15. Dixon B, van Erp SHM, Rodrigues PNS, Egberts E, Stet RJ (1995) Dev Comp Immunol 19:109–133

    Article  CAS  Google Scholar 

  16. Harstad H, Lukacs MF, Bakke HG, Grimholt U (2008) BMC Genomics 9:193

    Article  Google Scholar 

  17. Kjoglum S, Larsen S, Bakke HG, Grimholt U (2006) Fish Shellfish Immunol 21:431–441

    Article  CAS  Google Scholar 

  18. Jorgensen SM, Syvertsen BL, Lukacs M, Grimholt U, Gjoen T (2006) Fish Shellfish Immunol 21:548–560

    Article  CAS  Google Scholar 

  19. Rakus KL, Wiegertjes GF, Adamek M, Siwicki AK, Lepa A, Irnazarow I (2009) Fish Shellfish Immunol 26:737–743

    Article  CAS  Google Scholar 

  20. Kjoglum S, Larsen S, Bakke HG, Grimholt U (2008) Scand J Immunol 67:160–168

    Article  CAS  Google Scholar 

  21. Wynne JW, Cook MT, Nowak BF, Elliott NG (2007) Fish Shellfish Immunol 22:707–717

    Article  CAS  Google Scholar 

  22. Xu JY, Chen SL, Ding H (2009) J Fish Dis 32:637–640

    Article  CAS  Google Scholar 

  23. Fishpathogens database (2009) European Community Reference Laboratory for Fish Diseases (http://www.crl-fish.eu/)

  24. Stet RJ, Dixon B, Van Erp SHM, Van Lierop MJC, Rodrigues PNS, Egberts E (1996) Fish Shellfish Immunol 6:305–318

    Article  Google Scholar 

  25. Grimholt U, Drablos F, Jorgensen SM, Hoyheim B, Stet RJ (2002) Immunogenetics 54:570–581

    Article  CAS  Google Scholar 

  26. Sato A, Figueroa F, Murray BW, Malaga-Trillo E, Zaleska-Rutczynska Z, Sultmann H, Toyosawa S, Wedekind C, Steck N, Klein J (2000) Immunogenetics 51:108–116

    Article  CAS  Google Scholar 

  27. Phillips RB, Zimmerman A, Noakes MA, Palti Y, Morasch MR, Eiben L, Ristow SS, Thorgaard GH, Hansen JD (2003) Immunogenetics 55:561–569

    Article  CAS  Google Scholar 

  28. Zhao H, Stet RJ, Skjodt K, Savelkoul HF (2008) Fish Shellfish Immunol 24:459–466

    Article  CAS  Google Scholar 

  29. Stet RJ, Kruiswijk CP, Dixon B (2003) Crit Rev Immunol 23:441–471

    Article  CAS  Google Scholar 

  30. Miller KM, Li S, Ming TJ, Kaukinen KH, Schulze AD (2006) Immunogenetics 58:571–589

    Article  CAS  Google Scholar 

  31. Ruiz I, Fernández AB, de Blas I (2003) Aquatic 18:33–38

    Google Scholar 

  32. Elliott T, Williams A (2005) Immunol Rev 207:89–99

    Article  CAS  Google Scholar 

  33. Leng Q, Bentwich Z (2002) Scand J Immunol 56:224–232

    Article  CAS  Google Scholar 

  34. Bryant P, Ploegh H (2004) Curr Opin Immunol 16:96–102

    Article  CAS  Google Scholar 

  35. Rocha N, Neefjes J (2008) EMBO J 27:1–5

    Article  CAS  Google Scholar 

  36. Buonocore F, Randelli E, Casani D, Costantini S, Facchiano A, Scapigliati G, Stet RJ (2007) Fish Shellfish Immunol 23:853–866

    Article  CAS  Google Scholar 

  37. Costantini S, Buonocore F, Facchiano AM (2008) Fish Shellfish Immunol 25:782–790

    Article  CAS  Google Scholar 

  38. Hao HF, Li XS, Gao FS, Wu WX, Xia C (2007) Protein Expr Purif 51:120–125

    Article  CAS  Google Scholar 

  39. Stevens J, Wiesmuller KH, Walden P, Joly E (1998) Eur J Immunol 28:1272–1279

    Article  CAS  Google Scholar 

  40. Zhao H, Hermsen T, Stet RJ, Skjodt K, Savelkoul HF (2008) Mol Immunol 45:1658–1664

    Article  CAS  Google Scholar 

  41. Fujiki K, Smith CM, Liu L, Sundick RS, Dixon B (2003) Dev Comp Immunol 27:377–391

    Article  CAS  Google Scholar 

  42. Bremnes B, Rode M, Gedde-Dahl M, Nordeng TW, Jacobsen J, Ness SA, Bakke O (2000) Exp Cell Res 259:360–369

    Article  CAS  Google Scholar 

  43. Rudolph MG, Speir JA, Brunmark A, Mattsson N, Jackson MR, Peterson PA, Teyton L, Wilson IA (2001) Immunity 14:231–242

    Article  CAS  Google Scholar 

  44. Stern LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG, Strominger JL, Wiley DC (1994) Nature 368:215–221

    Article  CAS  Google Scholar 

  45. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Bioinformatics 23:2947–2948

    Article  CAS  Google Scholar 

  46. Arnold K, Bordoli L, Kopp J, Schwede T (2006) Bioinformatics 22:195–201

    Article  CAS  Google Scholar 

  47. Dunbrack RL Jr, Cohen FE (1997) Protein Sci 6:1661–1681

    Article  CAS  Google Scholar 

  48. Madden DR, Garboczi DN, Wiley DC (1993) Cell 75:693–708

    Article  CAS  Google Scholar 

  49. Knapp B, Omasits U, Schreiner W (2008) Protein Sci 17:977–982

    Article  CAS  Google Scholar 

  50. Knapp B, Omasits U, Frantal S, Schreiner W (2009) J Comput Aided Mol Des 23:301–307

    Article  CAS  Google Scholar 

  51. Rognan D, Stryhn A, Fugger L, Lyngbaek S, Engberg J, Andersen PS, Buus S (2000) J Comput Aided Mol Des 14:53–69

    Article  CAS  Google Scholar 

  52. Rammensee HG, Bachmann J, Emmerich NN, Bachor OA, Stevanovic S (1999) Immunogenetics 50:213–219

    Article  CAS  Google Scholar 

  53. Case DA, Darden TA, Cheatham I TE, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Pearlman DA, Crowley M, Walker RC, Zhang W, Wang B, Hayik S, Roitberg A, Seabra G, Wong KF, Paesani F, Wu X, Brozell S, Tsui V, Gohlke H, Yang L, Tan C, Mongan J, Hornak V, Cui G, Beroza P, Mathews DH, Schafmeister C, Ross WS, Kollman PA (2006) AMBER 9. University of California, San Francisco

  54. Li H, Robertson AD, Jensen JH (2005) Proteins 61:704–721

    Article  CAS  Google Scholar 

  55. Schutz CN, Warshel A (2001) Proteins 44:400–417

    Article  CAS  Google Scholar 

  56. Swanson JMJ, Adcock SA, McCammon JA (2005) J Chem Theory Comput 1:484–493

    Article  CAS  Google Scholar 

  57. Sitkoff D, Sharp KA, Honig B (1994) J Phys Chem 98:1978–1988

    Article  CAS  Google Scholar 

  58. Froloff N, Windemuth A, Honig B (1997) Protein Sci 6:1293–1301

    Article  CAS  Google Scholar 

  59. Pickett SD, Stenberg MJE (1993) J Mol Biol 231:825–839

    Article  CAS  Google Scholar 

  60. Doig AJ, Stenberg MJE (1995) Prot Sci 4:2247–2251

    Article  CAS  Google Scholar 

  61. Chang CE, Chen W, Gilson MK (2007) Proc Natl Acad Sci USA 104:1534–1539

    Article  CAS  Google Scholar 

  62. Chen W, Chang CE, Gilson MK (2004) Biophys J 87:3035–3049

    Article  CAS  Google Scholar 

  63. Schneider TD, Stephens RM (1990) Nucleic Acids Res 18:6097–6100

    Article  CAS  Google Scholar 

  64. Crooks GE, Hon G, Chandonia JM, Brenner SE (2004) Genome Res 14:1188–1190

    Article  CAS  Google Scholar 

  65. Kabsch W, Sander C (1983) Biopolymers 22:2577–2637

    Article  CAS  Google Scholar 

  66. Zhou H, Zhou Y (2002) Protein Sci 11:2714–2726

    Article  CAS  Google Scholar 

  67. Benkert P, Tosatto SC, Schomburg D (2008) Proteins 71:261–277

    Article  CAS  Google Scholar 

  68. Madden DR (1995) Annu Rev Immunol 13:587–622

    Article  CAS  Google Scholar 

  69. Cardenas C, Villaveces JL, Bohorquez H, Llanos E, Suarez C, Obregon M, Patarroyo ME (2004) Biochem Biophys Res Commun 323:1265–1277

    Article  CAS  Google Scholar 

  70. Cardenas C, Villaveces JL, Suarez C, Obregon M, Ortiz M, Patarroyo ME (2005) J Struct Biol 149:38–52

    Article  CAS  Google Scholar 

  71. Cardenas C, Ortiz M, Balbin A, Villaveces JL, Patarroyo ME (2005) Biochem Biophys Res Commun 330:1162–1167

    Article  CAS  Google Scholar 

  72. Cardenas C, Obregon M, Balbin A, Villaveces JL, Patarroyo ME (2007) J Mol Graph Model 25:605–615

    Article  CAS  Google Scholar 

  73. Wang J, Morin P, Wang W, Kollman PA (2001) J Am Chem Soc 123:5221–5230

    Article  CAS  Google Scholar 

  74. Lyne PD, Lamb ML, Saeh JC (2006) J Med Chem 49:4805–4808

    Article  CAS  Google Scholar 

  75. Stoica I, Sadiq SK, Coveney PV (2008) J Am Chem Soc 130:2639–2648

    Article  CAS  Google Scholar 

  76. Schafroth HD, Floudas CA (2004) Proteins 54:534–556

    Article  CAS  Google Scholar 

  77. Vita R, Zarebski L, Greenbaum JA, Emami H, Hoof I, Salimi N, Damle R, Sette A, Peters B (2010) Nucleic Acids Res 38:D854–D862

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We kindly acknowledge one of the reviewers for stimulating discussions. Financial support from the Spanish Ministerio de Ciencia e Innovación (SAF2008-05595), Generalitat de Catalunya (2009-SGR00298), and Chilean grant 07CN13PBT165 INNOVA-CORFO, and computational facilities from the Barcelona Supercomputer Center are also acknowledged. CC was partially supported by the Bicentennial Program PSD-08 (CONICYT/Chile).

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Authors and Affiliations

  1. Laboratorio de Genética e Inmunología Molecular, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Chile, Av. Brasil 2950, Valparaiso, Chile

    Constanza Cárdenas

  2. Laboratorio de Genética e Inmunología Molecular, Instituto de Biología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Chile, Av. Brasil 2950, Valparaiso, Chile

    Pablo Conejeros, Gloria Arenas & Sergio Marshall

  3. NBC-Núcleo de Biotecnología Curauma, Campus Curauma PUCV, Valparaiso, Chile

    Constanza Cárdenas, Pablo Conejeros, Gloria Arenas & Sergio Marshall

  4. Centro Regional Estudios Alimentación Saludable (CREAS), PUCV, Valparaiso, Chile

    Sergio Marshall

  5. Departament de Fisicoquímica and Institut de Biomedicina (IBUB), Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain

    Axel Bidon-Chanal & F. Javier Luque

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  1. Constanza Cárdenas
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Correspondence to Constanza Cárdenas, Sergio Marshall or F. Javier Luque.

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Cárdenas, C., Bidon-Chanal, A., Conejeros, P. et al. Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar . J Comput Aided Mol Des 24, 1035–1051 (2010). https://doi.org/10.1007/s10822-010-9387-8

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