Fig. 3

Consequences of impaired TWIST1/E12 (TE) dimerization on DNA binding. (a-b) 3D representation of the conserved TWIST1 (grey ribbon)/E12 (green ribbon) complex. Description of the position of the two series of residues (a) boxes A and D, and (b) B and C boxes, in the TE dimer are represented as a cartoon and CPK. The first dimerization blocs composed of boxes A and D (a), B and C (b) are represented by cylindrical grey and green solid surfaces, on the TWIST1 and E12 proteins, respectively. The localization of R154 on the TWIST1 ribbon is highlighted in CPK. c Evaluation of the impact of the R154P mutation on the number of H-bonds, in each individual box A to D by studing the percentage of variation of H-bond interactions between residues during TE and E R154P MD simulations, established between residue-residue and residue-DNA (R-R and R-base) or exclusively between residues (R-R). d Bar chart representing the variation of H-bond interactions between residues of the TE versus R154P TE complex. The sum of the interactions occurring between residues within the box A (left) and box B (right) of the wild type or mutated TWIST1 protein is highlighted. The percentage of cumulated occupancies of H-bond interactions occurring in the mutated R145P TE model is normalized against the TE model (100%). All cumulated occupancy values of the H-bonds were calculated as described in the Methods section. Briefly, H-bond interactions are assigned a value according to the distance between their atomic donors/acceptors during the 10 ns time-course of the MD simulation (interactions score 1 if their distance is under 2.1 Å, and 0 if above). Higher occupancy values being obtained for shorter and, therefore, more stable interactions. (SI function: SI(test_logic; value_if_true;value_if_false) with logic test:“<2.10”, value of 1 if true and 0 if false; NB.SI function: NB.SI(range;criterion))