The DNA-binding phenotype of the double mutant, Dri.SSS.ΔC, implies that the region C-terminal to the core ARID consensus, and amino acid identity at the major groove contact site, contribute to the presence of sequence specificity in ARID3 subfamily proteins, but do not support a conclusion that small amino acid differences, such as the identity of residues at the junction of Loop 2 and Helix 5, or the length of Loop 2, are the principal determinants of sequence specificity. Rather, the results suggest that overall differences in the three-dimensional structure of individual ARID subfamilies determines the presence of sequence specificity. A similar situation appears to hold for the distinction between sequence-specific and sequence-non-specific DNA binding in HMG domain proteins, considered further in the Discussion.
