JBIC Journal of Biological Inorganic Chemistry

, Volume 10, Issue 5, pp 463–475 | Cite as

Copper(II) complexes with chicken prion repeats: influence of proline and tyrosine residues on the coordination features

  • Diego La Mendola
  • Raffaele P. Bonomo
  • Giuseppe Impellizzeri
  • Giuseppe Maccarrone
  • Giuseppe Pappalardo
  • Adriana Pietropaolo
  • Enrico Rizzarelli
  • Valeria Zito
Original Article

Abstract

The prion protein (PrPc) is a copper-binding glycoprotein that can misfold into a β-sheet-rich and pathogenic isoform (PrPsc) leading to prion diseases. The first non-mammalian PrPc was identified in chicken and it was found to keep many structural motifs present in mammalian PrPc, despite the low sequence identity (approximately 40%) between the two primary structures. The present paper describes the synthesis and the coordination properties of some hexapeptide fragments (namely, PHNPGY , HNPGYP and NPGYPH) as well as a bishexapeptide (PHNPGYPHNPGY), which encompasses two hexarepeats. The copper(II) complexes were characterized by means of potentiometric, UV–vis, circular dichroism and electron paramagnetic resonance techniques. We also report the synthesis of three hexapeptides (PHNPGF, HNPGFP and NPGFPH), in which one tyrosine was replaced by phenylalanine as well as two bishexapeptides in which either one (PHNPGFPHNPGY and PHNPGYPHNPGF), or two tyrosines were replaced by phenylalanine, in order to check whether tyrosine was involved in copper(II) binding. Overall, the results indicate that the major copper(II) species formed by the chicken PrP dodecapeptides are stabler than the analogous species reported for the peptide fragments containing two octarepeat peptides from the mammalian prion protein. It is concluded that the presence of four prolyl residues, that are break points in copper coordination, induces the metal-assisted formation of macrochelates as well as the formation of binuclear species. Furthermore, it has been shown that the phenolic group is directly involved in the formation of copper binuclear species.

Keywords

Prion Copper(II) complexes Tandem hexarepeats Tyrosine 

Notes

Acknowledgements

This work was in part supported by the University of Catania, CNR Rome, and MIUR (PRIN-2003031424 and grant no.196 D.M. 1105/2002).

Supplementary material

775_2005_659_MOESM1_ESM.pdf (197 kb)
(PDF 198 KB)

References

  1. 1.
    Prusiner SB (1997) Science 278:245–251PubMedGoogle Scholar
  2. 2.
    Prusiner SB (1998) Cell 93:337–348PubMedGoogle Scholar
  3. 3.
    Brown DR, Qin KF, Herms JW, Madlung A, Manson J, Strome R, Fraser PE, Kruck T, Vonbohlen A, Schulzschaeffer W, Giese A, Westaway D, Kretzschmar H (1997) Nature 390:684–687PubMedADSGoogle Scholar
  4. 4.
    Lehmann S (2002) Curr Opin Chem Biol 6:187–192PubMedGoogle Scholar
  5. 5.
    Vassallo N, Herms J (2003) J Neurochem 86:538–544PubMedGoogle Scholar
  6. 6.
    Brown DR (2003) J Neurochem 87:377–385PubMedGoogle Scholar
  7. 7.
    Viles JH, Cohen FE, Prusiner SB, Goodin DB, Wright PE, Dyson HJ (1999) Proc Natl Acad Sci USA 96:2042–2046PubMedADSGoogle Scholar
  8. 8.
    Whittal RM, Ball HL, Cohen FE, Burlingame AL, Prusiner SB, Baldwin MA (2000) Protein Sci 9:332–343PubMedCrossRefGoogle Scholar
  9. 9.
    Millhauser GL (2004) Acc Chem Res 37:79–85PubMedGoogle Scholar
  10. 10.
    Jackson GS, Murray I, Hosszu LLP, Gibbs N, Waltho JP, Clarke AR, Collinge J (2001) Proc Natl Acad Sci USA 98:8531–8535PubMedADSGoogle Scholar
  11. 11.
    Kramer ML, Kratzin HD, Schmdt B, Romer A, Windl O, Liemann S, Hornemann S, Kretzschmar H (2001) J Biol Chem 276:16711–16719PubMedGoogle Scholar
  12. 12.
    Garnett AP, Viles JH (2003) J Biol Chem 278:6795–6802PubMedGoogle Scholar
  13. 13.
    Luczkowski M, Kozlowski H, Stawikowski M, Rolka K, Gaggelli E, Valensin D, Valensin G (2002) J Chem Soc Dalton Trans 2269–2275Google Scholar
  14. 14.
    Valensin D, Luczkowski M, Mancini FM, Legowska A, Gaggelli E, Valensin G, Rolka K, Kozlowski H (2004) J Chem Soc Dalton Trans 1284–1293Google Scholar
  15. 15.
    Harris DA, Falls DL, Johnson FA, Fischbach GD (1991) Proc Natl Acad Sci USA 88:7664–7668PubMedADSGoogle Scholar
  16. 16.
    Gabriel JM, Oesch B, Kretzschamer H, Scott M, Prusiner SB (1992) Proc Natl Acad Sci USA 89:9097–9101PubMedADSGoogle Scholar
  17. 17.
    Calzolai L, Lysek DA, Perez DR, Guntert P, Wuthrich K (2005) Proc Natl Acad Sci USA 102:651–655PubMedADSGoogle Scholar
  18. 18.
    Marcotte EM, Eisenberg D (1999) Biochemistry 38:667–676PubMedGoogle Scholar
  19. 19.
    Hornshaw MP, McDermott JR, Candy JM (1995) Biochem Biophys Res Commun 20:621–629Google Scholar
  20. 20.
    Hornshaw MP, McDermott JR, Candy JM, Lakey JH (1995) Biochem Biophys Res Commun 214:993–999PubMedGoogle Scholar
  21. 21.
    Pettit LD, Robbins RA (1995) In: Berthon G (ed) Handbook of metal–ligand interactions in biological fluids. Dekker, New York, pp 636–656Google Scholar
  22. 22.
    Bonomo RP, La Mendola D, Maccarrone G, Pappalardo G, Rizzarelli E (2003) J Inorg Biochem 96:190Google Scholar
  23. 23.
    Bonomo RP, Impellizzeri G, Pappalardo G, Rizzarelli E, Tabbì G (2000) Chem Eur J 6:4195–4202Google Scholar
  24. 24.
    Stanczak P, Luczkowski M, Juszczyk P, Grzonka Z, Kozlowski H (2004) J Chem Soc Dalton Trans 2102–2107Google Scholar
  25. 25.
    Arena G, Calì R, Rizzarelli E, Sammartano S (1976) Thermochim Acta 16:315Google Scholar
  26. 26.
    Gans P, Sabatini A, Vacca A (1996) Talanta 43:1739–1753PubMedGoogle Scholar
  27. 27.
    Bonomo RP, Calì R, Cucinotta V, Impellizzeri G, Rizzarelli E (1986) Inorg Chem 25:1641–1646Google Scholar
  28. 28.
    Gampp H, Maeder M, Meyer CJ, Zuberbuhler D (1985) Talanta 32:257–264Google Scholar
  29. 29.
    Bonomo RP, Bruno V, Conte E, De Guidi G, La Mendola D, Maccarroine G, Nicoletti F, Rizzarelli E, Sortino S, Vecchio G (2003) Dalton Trans 4406–4415Google Scholar
  30. 30.
    Hefford RJW, Pettit LD (1981) J Chem Soc Dalton Trans 1331–1335Google Scholar
  31. 31.
    Pettit LD, Steel I, Kovalik T, Kozlowski H, Bataille M (1985) J Chem Soc Dalton Trans 1201–1205Google Scholar
  32. 32.
    Livera C, Pettit LD, Bataille M, Krembel J, Bal W, Kozlowski H (1988) J Chem Soc Dalton Trans 1357–1360Google Scholar
  33. 33.
    Kiss T, Szucs Z (1986) J Chem Soc Dalton Trans 2443–2447Google Scholar
  34. 34.
    Kiss T (1987) J Chem Soc Dalton Trans 1263–1265Google Scholar
  35. 35.
    Brahmachari SK, Bhat TN, Sudhakar V, Vijayan M, Rapaka SR, Bhatnagar RS, Ananthanarayanan VS (1981) J Am Chem Soc 103:1703–1708Google Scholar
  36. 36.
    Zahn R, Liu A, Luhrs T, Riek R, Von Schroetter C, Lopez Garcia F, Billeter M, Calzolai L, Wider G, Wuthrich K (2000) Proc Natl Acad Sci USA 97:145–150PubMedADSGoogle Scholar
  37. 37.
    Lopez Garcia F, Zahn R, Riek R, Wuthrich K (2000) Proc Natl Acad Sci USA 97:8334–8339PubMedADSGoogle Scholar
  38. 38.
    Koslowski A, Sreerama N, Woody RW (2000) In: Berova N, Nakanishi K, Woody RW (eds) Circular dichroism. Wiley-VCH, New YorkGoogle Scholar
  39. 39.
    Woody RW (1996) In: Fasman GD (ed) Circular dichroism and the conformational analysis of biomolecules. Plenum, New YorkGoogle Scholar
  40. 40.
    Feller SM, Ren R, Hanafusa H, Baltimore D (1994) Trends Biochem Sci 19:453–458PubMedGoogle Scholar
  41. 41.
    Simon JA, Schreiber SL (1995) Chem Biol 2:53–60PubMedGoogle Scholar
  42. 42.
    Lee CH, Saksela K, Mirza UA, Chait BT, Kuriyan J (1996) Cell 85:931–942PubMedGoogle Scholar
  43. 43.
    Woody RW (1992) Adv Biophys Chem 2:37–79Google Scholar
  44. 44.
    Bienkiewicz E, Woody A-Y, Woody RW (2000) J Mol Biol 297:119–133PubMedGoogle Scholar
  45. 45.
    Dalcol I, Pons M, Ludevid MD, Giralt E (1996) J Org Chem 61:6775–6782PubMedGoogle Scholar
  46. 46.
    Petrella EC, Machesky LM, Kaiser DA, Polaard TD (1996) Biochemistry 35:16535–16543PubMedGoogle Scholar
  47. 47.
    Park SH, Shalongo W, Stellwagen E (1997) Protein Sci 6:1694–1700CrossRefPubMedGoogle Scholar
  48. 48.
    Kelly MA, Chellgren BW, Rucker AL, Troutman JM, Fried MG, Fried A-F, Creamer TP (2001) Biochemistry 40:14376–14383PubMedGoogle Scholar
  49. 49.
    Brookes G, Pettit LD (1975) J Chem Soc Dalton Trans 2106–2112Google Scholar
  50. 50.
    Pettit LD, Steel I, Formicka-Kozlowki G, Kozlowski H, Tatarowski T, Bataille M (1985) J Chem Soc Dalton Trans 535–539Google Scholar
  51. 51.
    Toni M, Massimino ML, Griffoni C, Salvato B, Tomasi V, Spisni E (2005) FEBS Lett 579:741–744PubMedGoogle Scholar
  52. 52.
    Matthews D, Cooke BC (2003) Rev Sci Tech 22:283–296PubMedGoogle Scholar
  53. 53.
    Lysek DA, Wuthrich K (2004) Biochemistry 43:10393–10399PubMedGoogle Scholar
  54. 54.
    Kovacs GG, Trabattoni G, Hainfellner JA, Ironside JW, Kinght RS, Budka H (2002) J Neurol 249:1567–1582PubMedGoogle Scholar

Copyright information

© SBIC 2005

Authors and Affiliations

  • Diego La Mendola
    • 1
  • Raffaele P. Bonomo
    • 2
  • Giuseppe Impellizzeri
    • 2
  • Giuseppe Maccarrone
    • 2
  • Giuseppe Pappalardo
    • 1
  • Adriana Pietropaolo
    • 2
  • Enrico Rizzarelli
    • 1
    • 2
  • Valeria Zito
    • 1
  1. 1.Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle RicercheSezione di CataniaCataniaItaly
  2. 2.Dipartimento di Scienze ChimicheUniversità di CataniaCataniaItaly

Personalised recommendations