Fig. 3. Structural analysis of p53 in complex with distinct REs.

a, b Binding modes of p53 in complex with low-affinity, K120R-unbound (a) and high-affinity, K120R-bound RE (b). Top left: schematic representation of tetrameric p53 and DNA interactions. The CWWG core motifs are highlighted in red or gold. The four Arg280 residues of tetrameric p53 (molecules I to IV) that interact with guanine of the CWWG core regions are marked as black lines. DNA sequence differences between 6FJ5²³ (a) and 3Q05¹⁴ (b) are shown in bold (positions 1, 8, 11, and 18). Lower left: overview of the p53 structure in complex with the respective RE. The 2F_o–F_c electron density map contoured at 1σ above the mean is shown for the L1 loops in green and for the Arg248 residues in brown. Right: detailed view of molecule I-DNA interactions. c Modeling the Lys120 to Arg (K120R) mutation in the binding mode of low-affinity, K120R-unbound REs suggests steric clashes, indicated by pink stars with two guanine bases at positions 2 and 3. d Left: superimposition of the DNAs of 6FJ5 (green) and 3Q05 (blue). Arrows indicate significant differences between the two DNA structures and the approximate positions of the Arg248 residues colored as in a and b sensing the minor groove width. The aligned sequences are shown on the bottom, with differences in the 20-bp regions highlighted in bold, and positions 3, 8, 13, and 18 underlined in red. Right: width of major (dashed) and minor grooves (solid) calculated by the program 3DNA^47,48. The plotted points correspond to positions between bps. Source data are provided as a Source Data file.