Fig. 6: Proposed mechanism for facilitated target DNA recognition by Meis1-HD.

(1) Free Meis1-HD (F) first non-specifically contacts DNA to form an anchor structure (NB) via the L1 loop, in a diffusion-controlled binding process. (2) Then, Meis1-HD rapidly translocates to the consensus DNA site by additional binding of α3 to form the specific binding state (SB), which is a facilitated binding process. (3) In the specific binding state, Meis1-HD exactly recognizes the consensus sequence by the conformational distortion and flexibility features of the DNA. A quantitative description of the energy landscape of the non-specific and specific binding states of Meis1-HD to WT and single-variant meisDNA is shown in the inset.