Solution structure of a peptide derived from the oncogenic protein β-Catenin in its phosphorylated and nonphosphorylated states

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2005-02, Vol.26 (2), p.227-241
• Main Authors: Megy, Simon, Bertho, Gildas, Gharbi-Benarous, Josyane, Baleux, Françoise, Benarous, Richard, Girault, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino Acid Sequence; beta Catenin; Binding Sites; Biochemistry, Molecular Biology; Biological and medical sciences; Circular Dichroism; Consensus Sequence; Cytoskeletal Proteins - chemistry; Fundamental and applied biological sciences. Psychology; Hydrocarbons, Fluorinated - chemistry; Hydrogen-Ion Concentration; Life Sciences; Models, Molecular; Molecular modeling; Molecular Sequence Data; NMR spectroscopy; Nuclear Magnetic Resonance, Biomolecular; Peptides - chemical synthesis; Peptides - chemistry; Peptides - isolation & purification; Phosphorylated peptide structure; Phosphorylation; Protein Conformation; Protein Folding; Protein Structure, Secondary; Serine - chemistry; Solutions; Spectrum Analysis, Raman; Trans-Activators - chemistry; Vertebrates: endocrinology; Water - chemistry; Wingless/Wnt signals; β-Catenin; β-TrCP
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2004.09.021

β-Catenin plays an essential role in the Wingless/Wnt signaling cascade. Phosphorylation of β-Catenin in its N-terminal region by the kinase GSK-3β is required for the interaction with the SCF-β-TrCP protein complex that targets β-Catenin for proteasome degradation. In the present work, we used two peptides of 32 amino acids referred to β-Cat 17–48 and P-β-Cat 17–48 for the phosphorylated peptide at the two sites Ser33 and Ser37. Circular dichroism and NMR techniques were used to assess the influence of the phosphorylation. The spectra of the peptides at pH 7.2 were completely assigned. Analysis of the medium-range NOE connectivities indicated that β-Cat 17–48 seems to be only poorly folded. These data are in agreement with the result of structure calculations. P-β-Cat 17–48 possesses two helical segments around the DpSGXXpS motif, which forms a large bent with the phosphate groups pointing out of the structure. On the contrary, β-Cat 17–48 shows less well-defined secondary structures and appears as a more flexible peptide, but adopts in the motif DSGXXS a more compact conformation than P-β-Cat 17–48. Differences in this molecular region suggest that conformational changes of phosphorylated β-Catenin play an important role for the interaction with the SCF-β-TrCP protein complex.