Preferences help
enabled [disable] Abstract
Number of results
2001 | 48 | 1 | 113-119
Article title

Cation binding properties of calretinin, an EF-hand calcium-binding protein.

Title variants
Languages of publication
Calretinin (CR) is a neuronal EF-hand protein previously characterized as a calcium (micromolar affinity) binding protein. CR-containing neurons are spared in some neurodegenerative diseases, although it is as yet unconfirmed how CR plays an active role in this protection. Higher levels of some metal cations (e.g. copper and zinc) are associated with these diseases. At the same time, metals such as terbium (NMR and fluorescence) cadmium (NMR) and manganese (EPR) serve as useful calcium analogues in the study of EF-hand proteins. We survey the binding of the above-mentioned metal cations that might affect the structure and function of CR. Competitive 45Ca2+-overlay, competitive terbium fluorescence and intrinsic tryptophan fluorescence are used to detect the binding of metal cations to CR. Terbium and copper (half-maximal effect of 15 μM) bind to CR. Terbium has a similar or greater affinity for the calcium-binding sites of CR than calcium. Copper quenches the fluorescence of terbium-bound CR, and CR tryptophan residues and competes weakly for 45Ca2+-binding sites. Cadmium, magnesium, manganese and zinc bind less strongly (half-maximal effects above 0.1 mM). Therefore, only terbium appears to be a suitable analytical calcium analogue in further studies of CR. The principal conclusion of this work is that copper, in addition to calcium, might be a factor in the function of CR and a link between CR and neurodegenerative diseases.

Physical description
  • Laboratory of Calcium-Binding Proteins, Nencki Institute of Experimental Biology, Warszawa, Poland
  • Laboratory of Calcium-Binding Proteins, Nencki Institute of Experimental Biology, Warszawa, Poland
  • 1. Rogers, J.H. (1987) Calretinin: A gene for a novel calcium-binding protein expressed principally in neurons [published erratum appears in J. Cell Biol. (1990) 110, 1845]. J. Cell Biol. 105, 1343-1353.
  • 2. Celio, M.R. (ed.) (1996) Guidebook to the Calcium-Binding Proteins. Sambrook & Tooze with OUP (Oxford).
  • 3. Cheung, W.T., Richards, D.E. & Rogers, J.H. (1993) Calcium binding by chick calretinin and rat calbindin D28k synthesised in bacteria. Eur. J. Biochem. 215, 401-410.
  • 4. Kuźnicki, J., Strauss, K.I. & Jacobowitz, D.M. (1995) Conformational changes and calcium binding by calretinin and its recombinant fragments containing different sets of EF hand motifs. Biochemistry 34, 15389-15394.
  • 5. Schwaller, B., Durussel, I., Jermann, D., Herrmann, B. & Cox, J.A. (1997) Comparison of the Ca2+-binding properties of human recombinant calretinin-22k and calretinin. J. Biol. Chem. 272, 29663-29671.
  • 6. Stevens, J. & Rogers, J.H. (1997) Chick calretinin: Purification, composition, and metal binding activity of native and recombinant forms. Protein Expr. Purif. 9, 171-181.
  • 7. Billing-Marczak, K. & Kuźnicki, J. (1999) Calretinin-sensor or buffer-function still unclear. Pol. J. Pharmacol. 51, 173-178.
  • 8. Edmonds, B., Reyes, R., Schwaller, B. & Roberts, W.M. (2000) Calretinin modifies presynaptic calcium signaling in frog saccular hair cells. Nat. Neurosci. 3, 786-790.
  • 9. Marilley, D. & Schwaller, B. (2000) Association between the calcium-binding protein calretinin and cytoskeletal components in the human colon adenocarcinoma cell line WiDr. Exp. Cell Res. 259, 12-22.
  • 10. Baudier, J. & Gerard, D. (1983) Ions binding to S100 proteins: Structural changes induced by calcium and zinc on S100a and S100b proteins. Biochemistry 22, 3360-3369.
  • 11. Baudier, J., Glasser, N. & Gerard, D. (1986) Ions binding to S100 proteins. I. Calcium- and zinc-binding properties of bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) protein: Zn2+ regulates Ca2+ binding on S100b protein. J. Biol. Chem. 261, 8192-8203.
  • 12. Filipek, A., Heizmann, C.W. & Kuźnicki, J. (1990) Calcyclin is a calcium and zinc binding protein. FEBS Lett. 264, 263-266.
  • 13. Heizmann, C.W. & Cox, J.A. (1998) New perspectives on S100 proteins: A multi-functional Ca(2+)-, Zn(2+)- and Cu(2+)-binding protein family. Biometals 11, 383-397.
  • 14. Nishikawa, T., Lee, I.S., Shiraishi, N., Ishikawa, T., Ohta, Y. & Nishikimi, M. (1997) Identification of S100b protein as copper-binding protein and its suppression of copper-induced cell damage. J. Biol. Chem. 272, 23037-23041.
  • 15. Shiraishi, N. & Nishikimi, M. (1998) Suppression of copper-induced cellular damage by copper sequestration with S100b protein. Arch. Biochem. Biophys. 357, 225-230.
  • 16. Permyakov, E.A., Kalinichenko, L.P., Derezhkov, V.Y., Antalik, M., Meinholtz, D.C. & Berliner, L.J. (1992) Interaction of cupric ion with parvalbumin. Biophys. Chem. 42, 189-194.
  • 17. Sayre, L.M., Perry, G. & Smith, M.A. (1999) Redox metals and neurodegenerative disease. Curr. Opin. Chem. Biol. 3, 220-225.
  • 18. Mouatt-Prigent, A., Agid, Y. & Hirsch, E.C. (1994) Does the calcium binding protein calretinin protect dopaminergic neurons against degeneration in Parkinson's disease? Brain Res. 668, 62-70.
  • 19. Chaudhuri, D., Horrocks, W.D., Jr., Amburgey, J.C. & Weber, D.J. (1997) Characterization of lanthanide ion binding to the EF-hand protein S100 beta by luminescence spectroscopy. Biochemistry 36, 9674-9680.
  • 20. Biekofsky, R.R., Muskett, F.W., Schmidt, J.M., Martin, S.R., Browne, J.P., Bayley, P.M. & Feeney, J. (1999) NMR approaches for monitoring domain orientations in calcium-binding proteins in solution using partial replacement of Ca2+ by Tb3+. FEBS Lett. 460, 519-526.
  • 21. Siedlecka, M., Goch, G., Ejchart, A., Sticht, H. & Bierzyński, A. (1999) Alpha-helix nucleation by a calcium-binding peptide loop. Proc. Natl. Acad. Sci. U.S.A. 96, 903-908.
  • 22. Bentrop, D., Bertini, I., Cremonini, M.A., Forsén, S., Luchinat, C. & Malmendal, A. (1997) Solution structure of the paramagnetic complex of the N-terminal domain of calmodulin with two Ce3+ ions by 1H NMR. Biochemistry 36, 11605-11618.
  • 23. Akke, M., Forsén, S. & Chazin, W.J. (1995) Solution structure of (Cd2+)1-calbindin D9k reveals details of the stepwise structural changes along the apo->(Ca2+)II1->(Ca2+)I,II2 binding pathway. J. Mol. Biol. 252, 102-121.
  • 24. Rustandi, R.R., Drohat, A.C., Baldisseri, D.M., Wilder, P.T. & Weber, D.J. (1998) The Ca(2+)-dependent interaction of S100B(beta beta) with a peptide derived from p53. Biochemistry 37, 1951- 1960.
  • 25. Strauss, K.I., Kuźnicki, J., Winsky, L. & Jacobowitz, D.M. (1994) Expression and rapid purification of recombinant rat calretinin: Similarity to native rat calretinin. Protein Expr. Purif. 5, 187- 191.
  • 26. Maruyama, K., Mikawa, T. & Ebashi, S. (1984) Detection of calcium binding proteins by 45Ca autoradiography on nitrocellulose membrane after sodium dodecyl sulfate gel elektrophoresis. J. Biochem. 95, 511-519.
  • 27. Veenstra, T.D., Gross, M.D., Hunziker, W. & Kumar, R. (1995) Identification of metal-binding sites in rat brain calcium-binding protein. J. Biol. Chem. 270, 30353-30358.
  • 28. Aquaron, R.R. & Wang, C.L. (1980) Binding of Ca2+ and Tb3+ to calmodulin. Ann. N. Y. Acad. Sci. 356, 354-355.
  • 29. Wang, C.L., Leavis, P.C., Horrocks, W.D., Jr. & Gergely, J. (1981) Binding of lanthanide ions to troponin C. Biochemistry 20, 2439-2444.
  • 30. Ma, C. & Opella, S.J. (2000) Lanthanide ions bind specifically to an added EF-Hand and orient a membrane protein in micelles for solution NMR spectroscopy. J. Magn. Reson. 146, 381-384.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.