The metal-binding properties of DREAM. Evidence for calcium-mediated changes in DREAM structure

Theodore A. Craig, Linda M. Benson, Sergei Yu Venyaminov, Elena S. Klimtchuk, Zeljko Bajzer, Franklyn G. Prendergast, Stephen Naylor, Rajiv Kumar

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

DREAM, an EF-hand protein, associates with and modulates the activity of presenilins and Kv4 potassium channels in neural and cardiac tissues and represses prodynorphin and c-fos gene expression by binding to DNA response elements in these genes. Information concerning the metal-binding properties of DREAM and the consequences of metal binding on protein structure are important in understanding how this protein functions in cells. We now show that DREAM binds 1 mol of calcium/mol of protein with relatively high affinity and another 3 mol of calcium with lower affinity. DREAM binds 1 mol of magnesium/mol of protein. DREAM, pre-loaded with 1 mol of calcium, binds 1 mol of magnesium, thus demonstrating that the magnesium-binding site is distinct from the high affinity calcium-binding site. Analysis of metal binding to mutant DREAM protein constructs localizes the high affinity calcium-binding site and the magnesium-binding site to EF-hands 3 or 4. Binding of calcium but not magnesium changes the conformation, stability, and a-helical content of DREAM. Calcium, but not magnesium, reduces the affinity of apo-DREAM for specific DNA response elements in the prodynorphin and c-fos genes. We conclude that DREAM binds calcium and magnesium and that calcium, but not magnesium, modulates DREAM structure and function.

Original languageEnglish (US)
Pages (from-to)10955-10966
Number of pages12
JournalJournal of Biological Chemistry
Volume277
Issue number13
DOIs
StatePublished - Mar 29 2002

Fingerprint

Magnesium
Metals
Calcium
Binding Sites
EF Hand Motifs
fos Genes
Proteins
Response Elements
Shal Potassium Channels
Genes
Presenilins
DNA
Mutant Proteins
Gene expression
Conformations
Carrier Proteins
Tissue
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Craig, T. A., Benson, L. M., Venyaminov, S. Y., Klimtchuk, E. S., Bajzer, Z., Prendergast, F. G., ... Kumar, R. (2002). The metal-binding properties of DREAM. Evidence for calcium-mediated changes in DREAM structure. Journal of Biological Chemistry, 277(13), 10955-10966. https://doi.org/10.1074/jbc.M109660200

The metal-binding properties of DREAM. Evidence for calcium-mediated changes in DREAM structure. / Craig, Theodore A.; Benson, Linda M.; Venyaminov, Sergei Yu; Klimtchuk, Elena S.; Bajzer, Zeljko; Prendergast, Franklyn G.; Naylor, Stephen; Kumar, Rajiv.

In: Journal of Biological Chemistry, Vol. 277, No. 13, 29.03.2002, p. 10955-10966.

Research output: Contribution to journalArticle

Craig, TA, Benson, LM, Venyaminov, SY, Klimtchuk, ES, Bajzer, Z, Prendergast, FG, Naylor, S & Kumar, R 2002, 'The metal-binding properties of DREAM. Evidence for calcium-mediated changes in DREAM structure', Journal of Biological Chemistry, vol. 277, no. 13, pp. 10955-10966. https://doi.org/10.1074/jbc.M109660200
Craig TA, Benson LM, Venyaminov SY, Klimtchuk ES, Bajzer Z, Prendergast FG et al. The metal-binding properties of DREAM. Evidence for calcium-mediated changes in DREAM structure. Journal of Biological Chemistry. 2002 Mar 29;277(13):10955-10966. https://doi.org/10.1074/jbc.M109660200
Craig, Theodore A. ; Benson, Linda M. ; Venyaminov, Sergei Yu ; Klimtchuk, Elena S. ; Bajzer, Zeljko ; Prendergast, Franklyn G. ; Naylor, Stephen ; Kumar, Rajiv. / The metal-binding properties of DREAM. Evidence for calcium-mediated changes in DREAM structure. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 13. pp. 10955-10966.
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