Fig. 1: Dual DNA-binding mode of Meis1-HD.
a Domain structure of human TF Meis1 and amino acid sequence of Meis1-HD. Numbering and secondary structure elements for Meis1-HD are shown on top of the sequence. The red color indicates TALE residues. b Residues of Meis1-HD involved in interaction with the consensus DNA duplex reported in a previous study12. Intermolecular hydrogen bonds are indicated by solid lines and van der Waals contacts are shown by open circles. c Sequence context of WT meisDNA. Orange bars indicate consensus base-pairs for Meis1 binding. d The ITC binding isotherm of Meis1-HD titrated into WT meisDNA at 298 K. Raw heat data (top) and the integrated heat data with the nonlinear regression fit (bottom) are shown. e Binding modes of Meis1-HD (denoted as M1) to a 10-bp DNA duplex: (i) first, M1 specifically binds to the consensus region to form an (M1)SB:DNA complex; (ii) and then an (M1)2:DNA complex is produced by non-specific binding of M1 to an (M1)SB:DNA complex. f Relative populations of free WT meisDNA (black) and the Meis1-HD–DNA complexes (M1SB:DNA (red), M1NB:DNA (green), or (M1)2:DNA (blue)) as a function of the [M1]t/[DNA]t ratio. g 1D imino spectrum of WT meisDNA at 298 K. h The exchange rate constants of the imino protons of the WT meisDNA–Meis1-HD complexes at various [M1]t/[DNA]t ratios. The error bars indicate the uncertainties associated with the curve fitting results. The asterisks indicate the kex value determined from the overlapped G2 and G4′ imino proton resonances. i (Upper) 1H chemical shift changes of the imino proton resonances and (lower) line width of the T3′ imino proton resonance in the WT meisDNA complexed with Meis1-HD as a function of the [M1]t/[DNA]t ratio.
