Encyclopedia of Metalloproteins

2013 Edition
| Editors: Robert H. Kretsinger, Vladimir N. Uversky, Eugene A. Permyakov

Copper-Binding Proteins

Reference work entry
DOI: https://doi.org/10.1007/978-1-4614-1533-6_126

Synonyms

Definition

Copper-binding proteins specifically incorporate the metal into their structure for catalytic and structural purposes. Noncatalytic, structural sites are found in copper sensing proteins involved in the regulation of copper metabolism and in copper sequestering peptides and proteins involved in protection against copper intoxication. The sensing proteins regulate all aspects of copper metabolism, including the uptake, intracellular use, detoxification, and export of copper. Commonly, the regulation is affected at the transcriptional level, and the binding of copper by the protein is the switch that modulates the sensor protein’s structure and function. The binding in these sites takes place through cysteinyl thiolates.

Noncatalytic Roles of Copper in Proteins

In noncatalytic proteins, copper serves a structural-regulatory role, a role mediated by its specific binding to sensory proteins where a change is elicited in the...

This is a preview of subscription content, log in to check access.

References

  1. Ahte P, Palumaa P, Tamm T (2009) Stability and conformation of polycopper-thiolate clusters studied by density functional approach. J Phys Chem A 113:9157–9164CrossRefPubMedGoogle Scholar
  2. Banci L, Bertini I, Ciofi-Baffoni S, Del Conte R, Gonnelli L (2003) Understanding copper trafficking in bacteria: interaction between the copper transport protein CopZ and the N-terminal domain of the copper ATPase CopA from Bacillus subtilis. Biochemistry 42:1939–1949CrossRefPubMedGoogle Scholar
  3. Brown KR, Keller GL, Pickering IJ, Harris HH, George GN, Winge DR (2002) Structures of the cuprous-thiolate clusters of the Mac1 and Ace1 transcriptional activators. Biochemistry 41:6469–6476CrossRefPubMedGoogle Scholar
  4. Cantini F, Banci L, Solioz M (2009) The copper-responsive repressor CopR of Lactococcus lactis is a ‘winged helix’ protein. Biochem J 417:493–499CrossRefPubMedGoogle Scholar
  5. Cobine P, Wickramasinghe WA, Harrison MD, Weber T, Solioz M, Dameron CT (1999) The Enterococcus hirae copper chaperone CopZ delivers copper(I) to the CopY repressor. FEBS Lett 445:27–30CrossRefPubMedGoogle Scholar
  6. Cobine PA, George GN, Jones CE, Wickramasinghe WA, Solioz M, Dameron CT (2002a) Copper transfer from the Cu(I) chaperone, CopZ, to the repressor Zn(II)CopY: metal coordination environments and protein interactions. Biochemistry 41:5822–5829CrossRefPubMedGoogle Scholar
  7. Cobine PA, Jones CE, Dameron CT (2002b) Role for zinc(II) in the copper(I) regulated protein CopY. J Inorg Biochem 88:192–196CrossRefPubMedGoogle Scholar
  8. Cotton FA, Wilkinson G, Murillo CA, Bochmann M (1999) Advanced Inorganic Chemistry. Wiley, New YorkGoogle Scholar
  9. Coyle P, Philcox JC, Carey LC, Rofe AM (2002) Metallothionein: the multipurpose protein. Cell Mol Life Sci 59:627–647CrossRefPubMedGoogle Scholar
  10. Dameron CT, Winge DR, George GN, Sansone M, Hu S, Hamer D (1991) A copper-thiolate polynuclear cluster in the ACE1 transcription factor. Proc Natl Acad Sci USA 88:6127–6131CrossRefPubMedGoogle Scholar
  11. Dameron CT, George GN, Arnold P, Santhanagopalan V, Winge DR (1993) Distinct metal binding configurations in ACE1. Biochemistry 32:7294–7301CrossRefPubMedGoogle Scholar
  12. Dobi A, Dameron CT, Hu S, Hamer D, Winge DR (1995) Distinct regions of Cu(I)-ACE1 contact two spatially resolved DNA major groove sites. J Biol Chem 270:10171–10176CrossRefPubMedGoogle Scholar
  13. Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 1:529–539CrossRefPubMedGoogle Scholar
  14. George GN, Winge D, Stout CD, Cramer SP (1986) X-ray absorption studies of the copper-beta domain of rat liver metallothionein. J Inorg Biochem 27:213–220CrossRefPubMedGoogle Scholar
  15. Green AR, Presta A, Gasyna Z, Stillman MJ (1994) Luminescent probe of copper-thiolate cluster formation within mammalian metallothionein. Inorg Chem 33:4159–4168CrossRefGoogle Scholar
  16. Gregory P, Lewis R, Curnock S, Dyke K (1997) Studies of the repressor (Bla1) of beta-lactamase synthesis in Staphylococcus aureus. Mol Microbiol 24:1025–1037CrossRefPubMedGoogle Scholar
  17. Lu ZH, Solioz M (2001) Copper-induced proteolysis of the CopZ copper chaperone of Enterococcus hirae. J Biol Chem 276:47822–47827PubMedGoogle Scholar
  18. Lu ZH, Cobine P, Dameron CT, Solioz M (1999) How cells handle copper: a view from microbes. J Trace Elem Exp Med 12:347–360CrossRefGoogle Scholar
  19. Lu ZH, Dameron CT, Solioz M (2003) The Enterococcus hirae paradigm of copper homeostasis: copper chaperone turnover, interactions, and transactions. Biometals 16:137–143CrossRefPubMedGoogle Scholar
  20. Pazehoski KO, Collins TC, Boyle RJ, Jensen-Seaman MI, Dameron CT (2008) Stalking metal-linked dimers. J Inorg Biochem 102:522–531CrossRefPubMedGoogle Scholar
  21. Pazehoski KO, Cobine PA, Winzor DJ, Dameron CT (2011) Evidence for involvement of the C-terminal domain in the dimerization of the CopY repressor protein from Enterococcus hirae. Biochem Biophys Res Commun 406:183–187CrossRefPubMedGoogle Scholar
  22. Pickering IJ, George GN, Dameron CT, Kurz B, Winge DR, Dance IG (1993) X-ray absorption spectroscopy of cuprous-thiolate clusters in proteins and model systems. J Am Chem Soc 115:9498–9505CrossRefGoogle Scholar
  23. Portmann R, Poulsen KR, Wimmer R, Solioz M (2006) CopY-like copper inducible repressors are putative ‘winged helix’ proteins. Biometals 19:61–70CrossRefPubMedGoogle Scholar
  24. Rubino JT, Riggs-Gelasco P, Franz KJ (2010) Methionine motifs of copper transport proteins provide general and flexible thioether-only binding sites for Cu(I) and Ag(I). J Biol Inorg Chem 15:1033–1049CrossRefPubMedGoogle Scholar
  25. Samson SL, Gedamu L (1998) Molecular analyses of metallothionein gene regulation. Prog Nucleic Acid Res Mol Biol 59:257–288CrossRefPubMedGoogle Scholar
  26. Sharp PA (2003) Ctr1 and its role in body copper homeostasis. Int J Biochem Cell Biol 35:288–291CrossRefPubMedGoogle Scholar
  27. Sivasankar C, Sadhukhan N, Bera JK, Samuelson AG (2007) Is copper(i) hard or soft? A density functional study of mixed ligand complexes. New J Chem 31:385–393CrossRefGoogle Scholar
  28. Solioz M (2002) Role of proteolysis in copper homoeostasis. Biochem Soc Trans 30:688–691CrossRefPubMedGoogle Scholar
  29. Solioz M, Stoyanov JV (2003) Copper homeostasis in Enterococcus hirae. FEMS Microbiol Rev 27:183–195CrossRefPubMedGoogle Scholar
  30. Solioz M, Vulpe C (1996) CPx-type ATPase – a class of P-type ATPases that pump heavy metals. Trends Biol Sci 21:237–241Google Scholar
  31. Strausak D, Solioz M (1997) CopY is a copper-inducible repressor of the Enterococcus hirae copper ATPases. J Biol Chem 272:8932–8936CrossRefPubMedGoogle Scholar
  32. Thorvaldsen JL, Sewell AK, McCowen CL, Winge DR (1993) Regulation of metallothionein genes by the ACE1 and AMT1 transcription factors. J Biol Chem 268:12512–12518PubMedGoogle Scholar
  33. Winge DR, Dameron CT, George GN (1994) The metallothionein structural motif in gene expression. Adv Inorg Biochem 10:1–48PubMedGoogle Scholar
  34. Wunderli-Ye H, Solioz M (1999) Copper homeostasis in Enterococcus hirae. Adv Exp Med Biol 448:255–264CrossRefPubMedGoogle Scholar
  35. Xiao Z, Loughlin F, George GN, Howlett GJ, Wedd AG (2004) C-terminal domain of the membrane copper transporter Ctr1 from Saccharomyces cerevisiae binds four Cu(I) ions as a cuprous-thiolate polynuclear cluster: sub-femtomolar Cu(I) affinity of three proteins involved in copper trafficking. J Am Chem Soc 126:3081–3090CrossRefPubMedGoogle Scholar
  36. Zhang L, Pickering IJ, Winge DR, George GN (2008) X-ray absorption spectroscopy of cuprous-thiolate clusters in Saccharomyces cerevisiae metallothionein. Chem Biodivers 5:2042–2049CrossRefPubMedGoogle Scholar
  37. Zhou P, Thiele DJ (1993) Copper and gene regulation in yeast. Biofactors 4:105–115PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Chemistry DepartmentSaint Francis UniversityLorettoUSA