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Fig. 5 | BMC Structural Biology

Fig. 5

From: Destabilization of the TWIST1/E12 complex dimerization following the R154P point-mutation of TWIST1: an in silico approach

Fig. 5

Consequences of impaired TWIST1/E12 (TE) dimerization on DNA binding. a 3D in silico representation of the TE complex bound to DNA, carried out using the VMD 1.9.1 software. The proximal flanking (−1; −1*) and first (1*; 1*) bases of the E-box are represented in grey and green VDW, respectively. b-c The pie charts show the percentages of cumulated occupancy of H-bonds established between residues of TWIST1 (grey) and E12 (green) and DNA bases during the (b) TE and (c) R154P TE MD simulations. Occupancies of H-bonds established with the proximal flanking (−1 and −1*) bases are represented in yellow, while the bar charts highlight the exact residues binding to those bases. The H-bonds established with the first consensus bases of the E-box (1 and 1*) are represented in grey and green for the TWIST1 and the E12 residues, respectively. d-g Distribution of “specific” H-bonds established between residues and E-box bases in the (d) TE and (f) mutated R154P TE molecular dynamics simulations. The pie charts show percentages of the total rate of cumulated occupancy of specific H-bonds established during the MD simulations. Consensus bases and variable bases of the E-box sequences are represented in grey and pink, respectively. The bar charts highlight the specific residues binding to cytosine (+1) and (+1*) bases, and show their implication in the DNA binding affinity. The DNA sequences are represented for (e) the TE and (g) mutated R154P TE dimers. The arrows highlight the major base interactions for the TE complex (blue arrow) and mutated R154P TE complex (green arrow). h Western blot showing that the tethered TWIST1/E12 R154P dimer (input left panel) was not able to interact with the TE-box unlike the tethered TWIST1/E12 wild-type dimer, as assessed by Streptavidin/Biotin assays. Tethered TE and TE R154P dimers were transiently produced in Hela cells. The protein sizes were 99 kDa for the thetered dimer TE and 25 kDa for the TWIST1 protein

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