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Features of the interactions between the methyl-CpG motif and the arginine residues on the surface of MBD proteins

Abstract

Recognition of the methylated regions of the DNA plays an important role in the epigenetic processes. We analyze the interactions between the methylated DNA and the methyl-CpG-binding proteins using two models. The first model was built from a methylated or non-methylated cytosine, a guanine and an arginine residue in the experimental arrangement. We applied the M06L density functional method with a small, polarized double-ζ basis set for the geometry optimizations, and the MP2 method with polarized triple-ζ basis set for the energy calculations. The second model was built from two methylcytosines, guanines, guanidinium groups plus an additional carboxyl group in the experimental arrangement. We applied the B3LYP method with a small, polarized double-ζ basis set for the geometry optimizations and thermal corrections. The single-point energies were obtained from dual-hybrid dRPA75 and dRPA@PBE0 calculations supplemented by a moderately large polarized triple-ζ basis set. The hydration effects were modeled by adding explicit water molecules. These calculations revealed that the hydrophobic interaction has the largest contribution to the Gibbs interaction energy and turns the arginine side chains into hydrogen bonding position. Our results show that the translation of the protein along the DNA double helix is sterically hindered by the contact of its arginine side chains with the methyl groups of the methyl cytosines. This supports a hopping mechanism for the searching movement of the protein along the DNA.

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References

  1. 1.

    Smith ZD, Meissner A (2013) Nat Rev Genet 14:204–220

  2. 2.

    Jones PA (2012) Nat Rev Genet 13:484–492

  3. 3.

    Zhou VW, Goren A, Bernstein BE (2011) Nat Rev Genet 12:7–18

  4. 4.

    Rivera CM, Ren B (2013) Cell 155:39–55

  5. 5.

    Kundaje A, Meuleman W, Ernst J et al (2015) Nature 518:317–330

  6. 6.

    Heyn H, Esteller M (2012) Nat Rev Genet 13:679–692

  7. 7.

    Lister R, Pelizzola M, Dowen RH et al (2009) Nature 462:315–322

  8. 8.

    Varley KE, Gertz J, Bowling KM et al (2013) Genome Res 23:555–567

  9. 9.

    Ziller MJ, Gu H, Müller F et al (2013) Nature 500:477–481

  10. 10.

    Bird A (2002) Genes Dev 16:6–21

  11. 11.

    Schübeler D (2015) Nature 517:321–326

  12. 12.

    Lister R, Mukamel EA, Nery JR et al (2013) Science 341:1237905

  13. 13.

    Schultz MD, He Y, Whitaker JW et al (2015) Nature 523:212–216

  14. 14.

    Jones PA, Takai D (2001) Science 293:1068–1070

  15. 15.

    Bird A (1992) Cell 70:5–8

  16. 16.

    Bird AP (1986) Nature 321:209–213

  17. 17.

    Gardiner-Garden M, Frommer M (1987) J Mol Biol 196:261–282

  18. 18.

    Larsen F, Gundersen G, Lopez R, Prydz H (1992) Genomics 13:1095–1107

  19. 19.

    Delgado S, Gómez M, Bird A, Antequera F (1998) EMBO J 17:2426–2435

  20. 20.

    Goll MG, Bestor TH (2005) Annu Rev Biochem 74:481–514

  21. 21.

    Schermelleh L, Haemmer A, Spada F et al (2007) Nucleic Acids Res 35:4301–4312

  22. 22.

    Spada F, Haemmer A, Kuch D et al (2007) J Cell Biol 176:565–571

  23. 23.

    Okano M, Bell DW, Haber DA, Li E (1999) Cell 99:247–257

  24. 24.

    Macleod D, Charlton J, Mullins J, Bird AP (1994) Genes Dev 8:2282–2292

  25. 25.

    Brandeis M, Frank D, Keshet I et al (1994) Nature 371:435–438

  26. 26.

    Han L, Lin IG, Hsieh C-L (2001) Mol Cell Biol 21:3416–3424

  27. 27.

    Rottach A, Leonhardt H, Spada F (2009) J Cell Biochem 108:43–51

  28. 28.

    Barreto G, Schäfer A, Marhold J et al (2007) Nature 445:671–675

  29. 29.

    Rai K, Huggins IJ, James SR et al (2008) Cell 135:1201–1212

  30. 30.

    Métivier R, Gallais R, Tiffoche C et al (2008) Nature 452:45–50

  31. 31.

    Schmitz K-M, Schmitt N, Hoffmann-Rohrer U et al (2009) Mol Cell 33:344–353

  32. 32.

    Ma DK, Jang M, Guo JU et al (2009) Science 323:1074–1077

  33. 33.

    Wu H, Zhang Y (2014) Cell 156:45–68

  34. 34.

    Williams K, Christensen J, Helin K (2011) EMBO Rep 13:28–35

  35. 35.

    Jones PL, Veenstra GJ, Wade PA et al (1998) Nat Genet 19:187–191

  36. 36.

    Nan X, Ng HH, Johnson CA et al (1998) Nature 393:386–389

  37. 37.

    Liu Y, Zhang X, Blumenthal RM, Cheng X (2013) Trends Biochem Sci 38:177–183

  38. 38.

    Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M (2008) Nature 455:818–821

  39. 39.

    Avvakumov GV, Walker JR, Xue S et al (2008) Nature 455:822–825

  40. 40.

    Hashimoto H, Horton JR, Zhang X, Bostick M, Jacobsen SE, Cheng X (2008) Nature 455:826–829

  41. 41.

    Hendrich B, Tweedie S (2003) Trends Genet 19:269–277

  42. 42.

    Ropero S, Fraga MF, Ballestar E et al (2006) Nat Genet 38:566–569

  43. 43.

    Amir RE, Van Den Veyver IB, Wan M, Tran CQ, Francke U (1999) Nat Genet 23:185–188

  44. 44.

    Sharma S, Kelly TK, Jones PA (2010) Carcinogenesis 31:27–36

  45. 45.

    Hassler MR, Egger G (2012) Biochimie 94:2219–2230

  46. 46.

    Jones PA, Laird PW (1999) Nat Genet 21:163–167

  47. 47.

    Lund AH, van Lohuizen M (2004) Genes Dev 18:2315–2335

  48. 48.

    Kanwal R, Gupta S (2010) J Appl Physiol 109:598–605

  49. 49.

    Esteller MN (2008) Engl J Med 358:1148–1159

  50. 50.

    Esteller M, Corn PG, Baylin SB, Herman JG (2001) Cancer Res 61:3225–3229

  51. 51.

    Lu J, Getz G, Miska EA et al (2005) Nature 435:834–838

  52. 52.

    Saito Y, Liang G, Egger G et al (2006) Cancer Cell 9:435–443

  53. 53.

    Lujambio A, Ropero S, Ballestar E et al (2007) Cancer Res 67:1424–1429

  54. 54.

    Lopez-Serra L, Esteller M (2008) Br J Cancer 98:1881–1885

  55. 55.

    Georgel PT, Horowitz-Scherer RA, Adkins N et al (2003) J Biol Chem 278:32181–32188

  56. 56.

    Jorgensen HF, Ben-Porath I, Bird AP (2004) Mol Cell Biol 24:3387–3395

  57. 57.

    Nikitina T, Shi X, Ghosh RP et al (2007) Mol Cell Biol 27:864–877

  58. 58.

    Baubec T, Ivánek R, Lienert F, Schübeler D (2013) Cell 153:480–492

  59. 59.

    Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M (2001) Cell 105:487–497

  60. 60.

    Ohki I, Shimotake N, Fujita N, Nakao M, Shirakawa M (1999) EMBO J 18:6653–6661

  61. 61.

    Inomata K, Ohki I, Tochio H, Fujiwara K, Hiroaki H, Shirakawa M (2008) Biochemistry 47:3266–3271

  62. 62.

    Walavalkar NM, Cramer JM, Buchwald WA et al (2015) Nucleic Acids Res 42:11218–11232

  63. 63.

    Wakefield RI, Smith BO, Nan X et al (1999) J Mol Biol 291:1055–1065

  64. 64.

    Scarsdale JN, Webb HD, Ginder GD, Williams DC (2011) Nucleic Acids Res 39:6741–6752

  65. 65.

    Ballestar E, Wolffe AP (2001) Eur J Biochem 268:1–6

  66. 66.

    Clouaire T, Stancheva I (2008) Cell Mol Life Sci 65:1509–1522

  67. 67.

    Fraga MF, Ballestar E, Montoya G et al (2003) Nucleic Acids Res 31:1765–1774

  68. 68.

    Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A (1999) Nature 401:301–304

  69. 69.

    Tatematsu K, Yamazaki T, Ishikawa F (2000) Genes Cells 5:677–688

  70. 70.

    Rooman M, Liévin J, Buisine E, Wintjens R (2002) J Mol Biol 319:67–76

  71. 71.

    Biot C, Wintjens R, Rooman M (2004) J Am Chem Soc 126:6220–6221

  72. 72.

    Zou X, Ma W, Solov’yov IA, Chipot C, Schulten K (2012) Nucleic Acids Res 40:2747–2758

  73. 73.

    Buisine E, Rooman M, Lie J (2002) J Mol Biol 2836:67–76

  74. 74.

    Ho KL, McNae IW, Schmiedeberg L et al (2008) Mol Cell 29:525–531

  75. 75.

    Mezei PD, Csonka GI, Ruzsinszky A, Kállay M (2015) J Chem Theory Comput 11:4615–4626

  76. 76.

    Mezei PD, Csonka GI (2015) Struct Chem 26:1367–1376

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Correspondence to Pál D. Mezei.

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Mezei, P.D., Csonka, G.I. Features of the interactions between the methyl-CpG motif and the arginine residues on the surface of MBD proteins. Struct Chem 27, 1317–1326 (2016). https://doi.org/10.1007/s11224-016-0783-0

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Keywords

  • Epigenetics
  • Methylated DNA
  • Hydration
  • Density functional theory
  • Random phase approximation