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Zn- and Cu-thioneins: a functional classification for metallothioneins?

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Abstract

This report intends to provide the reader with a deeper insight in the chemical, and extensively biological, characteristics of the metallothionein (MT) system. We have devoted nearly 20 years to the study of MTs and this has allowed us to form what we believe is a more complete picture of this peculiar family of metalloproteins. At the beginning of the 1990s, the landscape of this field was quite different from the overall picture we have now. Many researchers have contributed to the readjustment of this part of scientific knowledge. In our case, we implemented a unified method for obtaining MTs, for characterizing their metal-binding features, and for applying a unified research rationale. All this has helped to enlarge the initial picture that was mainly dominated by mammalian MT1/MT2 and yeast Cup1, by introducing approximately 20 new MTs. It has also allowed some characteristics to be clarified and examined in more detail, such as the cooperativity or the coexistence of multiple species in the metal-substitution reactions, the availability of Ag(I) or Cd(II) for use as respective probes for the Cu(I) and Zn(II) binding sites, the participation of chloride or sulfide ligands in the metal coordination spheres, and the feasibility of using in vitro data as representative of in vivo scenarios. Overall, the results yield enough data to consider new criteria for a proposal of classification of MTs based on MT metal-binding features, which complements the previous classifications, and that can shed light on the still controversial physiological functions of this peculiar superfamily of metalloproteins.

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References

  1. Margoshes M, Vallee B (1957) J Am Chem Soc 79:4813–4814

    Article  CAS  Google Scholar 

  2. Kägi JHR, Vallee BL (1960) J Biol Chem 235:3460–3465

    PubMed  Google Scholar 

  3. Lerch K, Ammer D, Olafson RW (1982) J Biol Chem 257:2420–2426

    PubMed  CAS  Google Scholar 

  4. Nemer M, Wilkinson DG, Travaglini EC, Sternberg EJ, Butt TR (1985) Proc Natl Acad Sci USA 82:4992–4994

    Article  PubMed  CAS  Google Scholar 

  5. Overnell J, Berger C, Wilson KJ (1981) Biochem Soc Trans 9:217–218

    CAS  Google Scholar 

  6. Kägi JHR, Nordberg M (eds) (1979) Metallothionein. Experientia supplementum, vol 34. Birkhäuser, Basel

  7. Kägi JHR, Kojima Y (eds) (1987) Metallothionein II: proceedings of the second international meeting on metallothionein and other low molecular weight metal-binding proteins. Experientia supplementum, vol. 52. Birkhäuser, Basel

  8. Dunn MA, Blalock TL, Cousins RJ (1987) Proc Soc Exp Biol Med 185:107–119

    PubMed  CAS  Google Scholar 

  9. Bremner I (1987) Prog Food Nutr Sci 11:1–37

    PubMed  CAS  Google Scholar 

  10. Hamer DH (1986) Annu Rev Biochem 55:913–951

    Article  PubMed  CAS  Google Scholar 

  11. Cousins RJ (1985) Physiol Rev 65:238–309

    PubMed  CAS  Google Scholar 

  12. Vasak M, Kagi JHR (1983) Met Ions Biol Syst 15:213–273

    CAS  Google Scholar 

  13. Brady FO (1982) Trends Biochem Sci 7:143–145

    Article  CAS  Google Scholar 

  14. http://www.uniprot.org. Accessed 22 Mar 2011

  15. Riordan JF, Vallee BL (1991) Methods in enzymology, vol. 205. Metallobiochemistry part B. Metallothionein and related molecules. Academic Press, San Diego

    Google Scholar 

  16. Fowler BA, Hildebrand CF, Kojima Y, Webb M (1987) In: Kägi JHR, Kojima Y (eds) Metallothionein II, vol 52. Birkhaüser, Basel, pp 19–22

  17. Capdevila M, Bofill R, Palacios Ò, Atrian S (2011) Coord Chem Rev. doi:10.1016/j.ccr.2011.07.006

  18. Murooka Y, Nagaoka T (1987) Appl Environ Microbiol 53:204–207

    PubMed  CAS  Google Scholar 

  19. Hou YM, Kim R, Kim SH (1988) Biochim Biophys Acta 951:230–234

    PubMed  CAS  Google Scholar 

  20. Romeyer FM, Jacobs FA, Masson L, Hanna Z, Brousseau R (1988) J Biotechnol 8:207–220

    Article  CAS  Google Scholar 

  21. Jacobs FA, Romeyer FM, Beauchemin M, Brousseau R (1989) Gene 83:95–103

    Article  PubMed  CAS  Google Scholar 

  22. Yamazaki S, Nakanishi M, Hamamoto T, Hirata H, Ebihara A, Tokue A, Kagawa Y (1992) Biochem Int 28:451–460

    PubMed  CAS  Google Scholar 

  23. Wang Y, Mackay EA, Kurasaki M, Kägi JHR (1994) Eur J Biochem 225:449–457

    Article  PubMed  CAS  Google Scholar 

  24. Cols N, Romero-Isart N, Capdevila M, Oliva B, Gonzàlez-Duarte P, Gonzàlez-Duarte R, Atrian S (1997) J Inorg Biochem 68:157–166

    Article  PubMed  CAS  Google Scholar 

  25. Palacios Ò, Pagani A, Pérez-Rafael S, Egg M, Höckner M, Brandstätter A, Capdevila M, Atrian S, Dallinger R (2011) BMC Biol 9:4

    Article  PubMed  CAS  Google Scholar 

  26. Orihuela R, Monteiro F, Pagani A, Capdevila M, Atrian S (2010) Chem Eur J 16:12363–12372

    Article  CAS  Google Scholar 

  27. Bofill R, Capdevila M, Cols N, Atrian S, González-Duarte P (2001) J Biol Inorg Chem 6:405–417

    Article  PubMed  CAS  Google Scholar 

  28. Palacios Ò, Polec-Pawlak K, Lobinski R, Capdevila M, González-Duarte P (2003) J Biol Inorg Chem 8:831–842

    Article  PubMed  CAS  Google Scholar 

  29. Tío L, Villarreal L, Atrian S, Capdevila M (2004) J Biol Chem 279:24403–24413

    Article  PubMed  Google Scholar 

  30. Valls M, Bofill R, Romero-Isart N, González-Duarte R, Abián J, Carrascal M, González-Duarte P, Capdevila M, Atrian S (2000) FEBS Lett 467:189–194

    Article  PubMed  CAS  Google Scholar 

  31. Domènech J, Palacios Ò, Villarreal L, González-Duarte P, Capdevila M, Atrian S (2003) FEBS Lett 533:72–78

    Article  PubMed  Google Scholar 

  32. Egli D, Domènech J, Selvaraj A, Balamurugan K, Hua H, Capdevila M, Georgiev O, Schaffner W, Atrian S (2006) Genes Cells 11:647–658

    Article  PubMed  CAS  Google Scholar 

  33. Guirola M, Naranjo Y, Capdevila M, Atrian S (2011) J Inorg Biochem 105:1050–1059

    Article  PubMed  CAS  Google Scholar 

  34. Valls M, Bofill R, González-Duarte R, González-Duarte P, Capdevila M, Atrian S (2001) J Biol Chem 276:32835–32843

    Article  PubMed  CAS  Google Scholar 

  35. Mir G, Domènech J, Huguet G, Guo W, Goldsbrough P, Atrian S, Molinas M (2004) J Exp Bot 55:2483–2493

    Article  PubMed  CAS  Google Scholar 

  36. Domènech J, Mir G, Huguet G, Capdevila M, Molinas M, Atrian S (2006) Biochimie 88:583–593

    Article  PubMed  Google Scholar 

  37. Domènech J, Orihuela R, Mir G, Molinas M, Atrian S, Capdevila M (2007) J Biol Inorg Chem 12:867–882

    Article  PubMed  Google Scholar 

  38. Villarreal L, Tío L, Capdevila M, Atrian S (2006) FEBS J 273:523–535

    Article  PubMed  CAS  Google Scholar 

  39. Pagani A, Villarreal L, Capdevila M, Atrian S (2007) Mol Microbiol 63:256–269

    Article  PubMed  CAS  Google Scholar 

  40. Domènech J, Bofill R, Tinti A, Torreggiani A, Atrian S, Capdevila M (2008) Biochim Biophys Acta 1784:693–704

    PubMed  Google Scholar 

  41. Orihuela R, Domènech J, Bofill R, You C, Mackay EA, Kägi JHR, Capdevila M, Atrian S (2008) J Biol Inorg Chem 13:801–812

    Article  PubMed  CAS  Google Scholar 

  42. Bofill R, Orihuela R, Romagosa M, Domenech J, Atrian S, Capdevila M (2009) FEBS J 276:7040–7056

    Article  PubMed  CAS  Google Scholar 

  43. Höckner M, Stefanon K, de Vaufleury A, Monteiro F, Pérez-Rafael S, Palacios Ò, Capdevila M, Atrian S, Dallinger R (2011) Biometals. doi:10.1007/s10534-011-9466-x

  44. Pérez-Rafael S, Mezger A, Lieb B, Dallinger R, Capdevila M, Palacios Ò, Atrian S (2011) J Inorg Biochem (submitted)

  45. Capdevila M, Cols N, Romero-Isart N, Gonzàlez-Duarte R, Atrian S, Gonzàlez-Duarte P (1997) Cell Mol Life Sci 53:681–688

    Article  PubMed  CAS  Google Scholar 

  46. Capdevila M, Romero N, Cols N, Atrian S, Stillman MJ, González-Duarte R, González-Duarte P (1996) Anal Quim Int Ed 92:199–201

    CAS  Google Scholar 

  47. Bofill R, Palacios O, Capdevila M, Cols N, González-Duarte R, Atrian S, González-Duarte P (1999) J Inorg Biochem 73:57–64

    Article  PubMed  CAS  Google Scholar 

  48. Cols N, Romero-Isart N, Bofill R, Capdevila M, González-Duarte P, González-Duarte R, Atrian S (1999) Prot Eng 12:265–269

    Article  CAS  Google Scholar 

  49. Romero-Isart N, Cols N, Termansen MK, Gelpi JL, Gonzalez-Duarte R, Atrian S, Capdevila M, Gonzalez-Duarte P (1999) Eur J Biochem 259:519–527

    Article  PubMed  CAS  Google Scholar 

  50. Polec-Pawlak K, Palacios Ò, Capdevila M, González-Duarte P, Lobinski R (2002) Talanta 57:1011–1017

    Article  PubMed  CAS  Google Scholar 

  51. Leiva-Presa A, Capdevila M, González-Duarte P (2004) Eur J Biochem 271:4872–4880

    Article  PubMed  CAS  Google Scholar 

  52. Stillman MJ (1995) Coord Chem Rev 144:461–511

    Article  CAS  Google Scholar 

  53. Nielson KB, Winge DR (1983) J Biol Chem 258:13063–13069

    PubMed  CAS  Google Scholar 

  54. Good M, Hollenstein R, Sadler PJ, Vasak M (1988) Biochem 27:7163–7166

    Article  CAS  Google Scholar 

  55. Vaher M, Romero-Isart N, Vasak M, Palumaa P (2001) J Inorg Biochem 83:1–6

    Article  PubMed  CAS  Google Scholar 

  56. Gehrig PM, You C, Dallinger R, Gruber C, Brouwer M, Kagi JHR, Hunziker PE (2000) Prot Sci 9:395–402

    Article  CAS  Google Scholar 

  57. Meloni G, Zovo K, Kazantseva J, Palumaa P, Vasak M (2006) J Biol Chem 281:14588–14595

    Article  PubMed  CAS  Google Scholar 

  58. Otvos JM, Armitage IM (1980) Proc Natl Acad Sci USA 77:7094–7098

    Article  PubMed  CAS  Google Scholar 

  59. Palacios O, Leiva-Presa A, Atrian S, Lobinki R (2007) Talanta 72:480–488

    Article  PubMed  CAS  Google Scholar 

  60. Vallee BL, Auld DS (1990) Biochemistry 29:5647–5659

    Article  PubMed  CAS  Google Scholar 

  61. Vasak M (1998) Biodegradation 9:501–512

    Article  PubMed  CAS  Google Scholar 

  62. Chang CC, Huang PC (1996) Protein Eng 9:1165–1172

    Article  PubMed  CAS  Google Scholar 

  63. Dance I, Fisher K, Lee G (1992) In: Stillman MJ, Shaw CF III, Suzuki KT (eds) Metallothioneins: synthesis, structure and properties of metallothioneins, phytochelatins, and metal–thiolate complexes. VCH, New York, pp 284–345

  64. Blindauer CA, Leszczyszyn OI (2010) Nat Prod Rep 27:720–741

    Article  PubMed  CAS  Google Scholar 

  65. Peterson CW, Narula SS, Armitage IM (1996) FEBS Lett 379:58–93

    Article  Google Scholar 

  66. Bertini I, Hartmann H-J, Klein T, Liu G, Luchinat C, Weser U (2000) Eur J Biochem 267:1008–1018

    Article  PubMed  CAS  Google Scholar 

  67. Calderone V, Dolderer B, Hartmann HJ, Echner H, Luchinat C, Del Bianco C, Mangani S, Weser U (2005) Proc Natl Acad Sci USA 102:51–56

    Article  PubMed  CAS  Google Scholar 

  68. Schultze P, Worgotter E, Braun W, Wagner G, Vasak M, Kagi JH, Wuthrich K (1988) J Mol Biol 203:251–268

    Article  PubMed  CAS  Google Scholar 

  69. Arseniev A, Schultze P, Worgotter E, Braun W, Wagner G, Vasak M, Kagi JH, Wuthrich K (1988) J Mol Biol 201:637–657

    Article  PubMed  CAS  Google Scholar 

  70. Capasso C, Carginale V, Crescenzi O, Di Maro D, Parisi E, Spadaccini R, Temussi PA (2003) Structure 11:435–443

    Article  PubMed  CAS  Google Scholar 

  71. Quaife CJ, Findley SD, Erickson JC, Froelick GJ, Kelly EJ, Zambrowicz BP, Palmiter RD (1994) Biochemistry 33:7250–7259

    Article  PubMed  CAS  Google Scholar 

  72. Dallinger R, Berger B, Hunziker PE, Kaegi JHR (1997) Nature 388:237–238

    Article  PubMed  CAS  Google Scholar 

  73. Hispard F, Schuler D, de Vaufleury A, Scheifler R, Badot PM, Dallinger R (2008) Environ Toxicol Chem 27:1533–1542

    Article  PubMed  CAS  Google Scholar 

  74. Blindauer CA, Harrison MD, Parkinson JA, Robinson AK, Cavet JS, Robinson NJ, Sadler PJ (2001) Proc Natl Acad Sci USA 98:9593–9598

    Article  PubMed  CAS  Google Scholar 

  75. Peroza EA, Schmucki R, Guntert P, Freisinger E, Zerbe O (2009) J Mol Biol 387:207–218

    Article  PubMed  CAS  Google Scholar 

  76. Maret W, HeVron G, Hill HA, Djuricic D, Jiang LJ, Vallee BL (2002) Biochemistry 41:1689–1694

    Article  PubMed  CAS  Google Scholar 

  77. Villarreal L, Tío L, Atrian S, Capdevila M (2005) Arch Biochem Biophys 435:331–335

    Article  PubMed  CAS  Google Scholar 

  78. Winge D, Dameron CT, Mehra RK (1992) In: Kägi JHR, Kojima Y (eds) Metallothionein II, vol 52. Birkhaüser, Basel, pp 257–270

  79. Dameron CT, Reese RN, Mehra RK, Kortan AR, Carroll PJ, Steigerwald ML, Brus LE, Winge DR (1989) Nature 338:596–597

    Article  CAS  Google Scholar 

  80. Capdevila M, Domènech J, Pagani A, Tío L, Villarreal L, Atrian S (2005) Angew Chem Int Ed 44:4618–4622

    Article  CAS  Google Scholar 

  81. Tío L, Villarreal L, Atrian S, Capdevila M (2006) Exp Bio Med 231:1522–1527

    Google Scholar 

  82. Bofill R, Capdevila M, Atrian S (2009) Metallomics 1:229–234

    Article  PubMed  CAS  Google Scholar 

  83. Strain J, Culotta VC (1996) Mol Gen Genet 251:139–145

    PubMed  CAS  Google Scholar 

  84. Outten FW, Huffman DL, Hale JA, O’Halloran TV (2001) J Biol Chem 276:30670–30677

    Article  PubMed  CAS  Google Scholar 

  85. Kägi JHR, Kojima Y (1987) Experientia supplementum, vol 52. Metallothionein II. Birkhäuser, Basel

    Google Scholar 

  86. http://www.bioc.unizh.ch/mtpage/classif.html. Accessed 22 March 2011

  87. Capdevila M, Palacios O, Atrian S (2010) Bioinorg Chem Appl 1–6. doi:10.1155/2010/541829

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Acknowledgments

We wish to thank the Spanish Ministerio de Ciencia e Innovación for its continued financial support, and particularly for the current projects BIO2009-12513-C02-01 to S.A. and BIO2009-12513-C02-02 to M.C. The authors are members of the Grup de Recerca de la Generalitat de Catalunya, reference 2009SGR-1457, and the COST Action (EU) CM0603 on Free Radicals in Chemical Biology.

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Correspondence to Mercè Capdevila.

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This article is part of a JBIC special issue on metallothioneins.

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Palacios, Ò., Atrian, S. & Capdevila, M. Zn- and Cu-thioneins: a functional classification for metallothioneins?. J Biol Inorg Chem 16, 991–1009 (2011). https://doi.org/10.1007/s00775-011-0827-2

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