such as HMG1 and HMG2 that bind DNA in a sequence-non-specific manner. These proteins generally contain two or more HMG domains (47,48). There is a high degree of sequence similarity and structural characteristics between the sequence-specific and the sequence-non-specific HMG domains in complex with DNA. Some highly conserved residues have been identified as very important in sequence specificity of HMG domains, but these residues alone are not the sole determinant of sequence specificity [reviewed in (47)]. Rather, sequence-specificity appears to be a combination of effects of residues on the domain's positioning, affinity, its stability in complex with DNA, the number of interactions on the protein–DNA interface and the number of base-specific contacts (49). Studies of the HMG domain indicate the difference between sequence-specific and sequence-non-specific members of the same family is generally more complex than the simple substitution of contact residues for neutral residues.
