The Ca(2+)-dependent interaction of S100B(beta beta) with a peptide derived from p53.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleThe Ca(2+)-dependent interaction of S100B(beta beta) with a peptide derived from p53.
Publication TypeJournal Article
Year of Publication1998
AuthorsRustandi, RR, Drohat, AC, Baldisseri, DM, Wilder, PT, Weber, DJ
Date Published1998 Feb 17
KeywordsAmino Acid Sequence, Animals, Calcium, Calcium-Binding Proteins, Humans, Manganese, Models, Molecular, Molecular Sequence Data, Nerve Growth Factors, Nuclear Magnetic Resonance, Biomolecular, Peptides, Phosphorylation, Protein Binding, Rats, S100 Proteins, Spectrometry, Fluorescence, Tumor Suppressor Protein p53

S100B(beta beta) was found to interact with the tumor suppressor protein, p53, and inhibit its PKC-dependent phosphorylation and tetramer formation [Baudier, J., Delphin, C., Grunwald, D., Khochbin, S., and Lawrence, J. J. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11627-11631]. Since PKC-dependent phosphorylation at the C-terminus of p53 is known to effect transcription and p53 tetramer formation [Sakaguchi, K., Sakamoto, H., Lewis, M. S., Anderson, C. W., Erickson, J. W., Appella, E., and Xie, D. (1997) Biochemistry 36, 10117-10124], we examined the interaction of S100B(beta beta) with a peptide derived from the C-terminal regulatory domain of p53 (residues 367-388). In this paper, we report that S100B(beta beta) binds to the p53 peptide (CaK3 < or = 23.5 +/- 6.6 microM) in a Ca(2+)-dependent manner, and that the presence of the p53 peptide was found to increase the binding affinity of Ca2+ to S100B(beta beta) by 3-fold using EPR and PRR methods, whereas the peptide had no effect on Zn2+ binding to S100B(beta beta). Fluorescence and NMR spectroscopy experiments show that the p53 peptide binds to a region of S100B(beta beta) that probably includes residues in the "hinge" (S41, L44, E45, E46, I47), C-terminal loop (A83, C84, H85, E86, F87, F88), and helix 3 (V52, V53, V56, T59). Together these data support the notion that S100B(beta beta) inhibits PKC-dependent phosphorylation by binding directly to the C-terminus of p53.

Alternate JournalBiochemistry
PubMed ID9485322
Grant ListR29GM52071 / GM / NIGMS NIH HHS / United States
S10RR10441 / RR / NCRR NIH HHS / United States