Figure 2: Rational engineering how reprogramming factors read genomes. ( a ) Dimeric MyoD structure bound to DNA (pdb-ID 1 mdy 98). The DNA is shown as a gray surface plot and the two MyoD molecules forming the dimer as yellow and brown cartoon. Residues engrafted from MyoD into E12 to turn E12 into a myogenic protein are shown as black ball-and-sticks and are highlighted with a dashed oval. ( b ) Structural models showing heterodimers of Oct4 (light blue) and Sox2 (yellow) on the canonical motif and Oct4-Sox17 (orange) on the compressed motif. Sox residues that determine the discriminative heterodimerization with Oct4 on canonical and compressed motifs are shown as black ball-and-sticks. Transplanting Lys57 from Sox2 into Sox17 alone turns Sox17 into a potent inducer of pluripotency.142 The structural models were constructed as described in 146 based on coordinates derived from pdb-IDs 3f27 and 1 gt0.129,130,145 To the right of the structural cartoons the domain structure of MyoD versus E12 and Sox2 versus Sox17 is compared. The percentages above the domain plots indicate the amino acid identity between the protein pairs in the N-terminal, DNA binding and C-terminal region. The alignment was performed using sequences derived from Uniprot: MyoD P10085; E12:P15806; Sox2:P48432; Sox17:Q61473. Oct4: octamer binding protein 4.