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

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-Cat17-48 and P-β-Cat17-48 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-Cat17-48 seems to be only poorly folded. These data are in agreement with the result of structure calculations. P-β-Cat17-48 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-Cat17-48 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-Cat17-48. 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.