Structure of the negative regulatory domain of p53 bound to S100B(ββ)

A Ca2+ dependent conformational change in dimeric S100B(ββ) is required for it to bind p53 and inhibit phosphorylation of this tumor suppressor in its C-terminal negative regulatory domain. A peptide derived from this region of p53 (residues 367–388) was found to have no regular structure in its native form by NMR spectroscopy, but becomes helical when bound to Ca2+ loaded S100B(ββ). The three-dimensional structure of this complex reveals several favorable hydrophobic and electrostatic interactions between S100B(ββ) and the p53 peptide in the binding pocket, where S100B(ββ) sterically blocks sites of phosphorylation and acetylation on p53 that are important for transcription activation.

[1]  Brendan D. Price,et al.  Regulation of the p53 Protein by Protein Kinase Cα and Protein Kinase Cζ , 1998 .

[2]  B. Sykes,et al.  Binding of cardiac troponin-I147-163 induces a structural opening in human cardiac troponin-C. , 1999, Biochemistry.

[3]  V. Gerke,et al.  The crystal structure of a complex of p11 with the annexin II N-terminal peptide. , 1999, Nature Structural Biology.

[4]  S. Grzesiek,et al.  Isotope-Filtered 2D HOHAHA Spectroscopy of a Peptide-Protein Complex Using Heteronuclear Hartmann-Hahn Dephasing , 1994 .

[5]  David J Weber,et al.  Solution structure of calcium-bound rat S100B(betabeta) as determined by nuclear magnetic resonance spectroscopy,. , 1998, Biochemistry.

[6]  David J Weber,et al.  The Ca2+-Dependent Interaction of S100B(ββ) with a Peptide Derived from p53† , 1998 .

[7]  G. Marius Clore,et al.  Refined solution structure of the oligomerization domain of the tumour suppressor p53 , 1995, Nature Structural Biology.

[8]  A. Bax,et al.  2D and 3D NMR Study of Phenylalanine Residues in Proteins by Reverse Isotopic Labeling , 1994 .

[9]  T. Davison,et al.  Characterization of the oligomerization defects of two p53 mutants found in families with Li–Fraumeni and Li–Fraumeni-like syndrome , 1998, Oncogene.

[10]  E. Gruenstein,et al.  Characterization of S-100b Binding Epitopes. IDENTIFICATION OF A NOVEL TARGET, THE ACTIN CAPPING PROTEIN, CapZ (*) , 1995, The Journal of Biological Chemistry.

[11]  D. Hilt,et al.  The S100 protein family. , 1988, Trends in biochemical sciences.

[12]  David J Weber,et al.  Structural changes in the C‐terminus of Ca2+‐bound rat S100B(ββ) upon binding to a peptide derived from the C‐terminal regulatory domain of p53 , 1999, Protein science : a publication of the Protein Society.

[13]  A. Levine.  p53, the Cellular Gatekeeper for Growth and Division , 1997, Cell.

[14]  K. Sakaguchi,et al.  DNA damage activates p53 through a phosphorylation-acetylation cascade. , 1998, Genes & development.

[15]  J. Baudier,et al.  Calcium and S100B Regulation of p53-Dependent Cell Growth Arrest and Apoptosis , 1998, Molecular and Cellular Biology.

[16]  C. Arrowsmith,et al.  Solution structure of the tetrameric minimum transforming domain of p53 , 1995, Nature Structural Biology.

[17]  David J Weber,et al.  S100B(ββ) inhibits the protein kinase C‐dependent phosphorylation of a peptide derived from p53 in a Ca2+‐dependent manner , 1998 .

[18]  D. Grunwald,et al.  Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  F. Richards,et al.  The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. , 1992, Biochemistry.

[20]  D. Beckett,et al.  Oligomerization state of S100B at nanomolar concentration determined by large‐zone analytical gel filtration chromatography , 1997, Protein science : a publication of the Protein Society.

[21]  V. Gerke,et al.  Structural basis of the Ca(2+)-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I. , 2000, Structure.

[22]  H. Sakamoto,et al.  Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. , 1997, Biochemistry.

[23]  Y. Kai,et al.  A novel mode of target recognition suggested by the 2.0 A structure of holo S100B from bovine brain. , 1998, Structure.

[24]  P. Jeffrey,et al.  Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. , 1994, Science.

[25]  G. Shaw,et al.  A novel calcium-sensitive switch revealed by the structure of human S100B in the calcium-bound form. , 1998, Structure.

[26]  David J Weber,et al.  The use of dipolar couplings for determining the solution structure of rat apo‐S100B(ββ) , 2008, Protein science : a publication of the Protein Society.

[27]  N. Pavletich,et al.  Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms , 1995, Science.

[28]  R. Donato,et al.  Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. , 1999, Biochimica et biophysica acta.

[29]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[30]  K. Sakaguchi,et al.  Calcium-dependent Interaction of S100B with the C-terminal Domain of the Tumor Suppressor p53* , 1999, The Journal of Biological Chemistry.