Inspection of the sequences in Figure 1 does not reveal any obvious distinction between sequence-specific and sequence-non-specific ARIDs. However, the structures of the MRF2, Dri and p270 ARIDs have been solved in complex with DNA (15,17,18). Each study agrees that a portion of the region encompassing Loop 2 and/or Helix 5 lies within the major groove (see Figure 5), and that regions upstream and/or downstream of the junction of Loop 2 and Helix 5 contact the minor groove. The results have generated some ideas about the basis for sequence specificity, but these have not yet been tested empirically. Iwahara et al. (18) studied the Dri ARID by NMR, and identified four residues in Loop 2 and Helix 5 of Dri that make base-specific interactions in the major groove of the DNA. These residues included two threonines (T), a serine (S) and a phenylalanine (F), and are underlined in the Dri ARID sequence shown in Figure 5. p270 has a serine (S) at each of the corresponding positions. This study suggested that the lack of the threonines and of a non-polar residue at the phenylalanine position underlies the lack of sequence specificity in p270.
