Homeodomain Proteins

Abstract As described in Chapter 3, homeodomain proteins are transcription factors that are characterized by the presence of a 60-amino-acid DNA binding domain. The structure of the homeodomain consists of a flexible amino-terminal arm followed by three a helices (Fig. 9.1) with the second and third helices forming a helix-turn-helix motif that is structurally similar to the DNA binding domain of several prokaryotic transcriptonal repressors (Harrison and Aggarwal, 1990). The carboxyl-terminal third helix of the homeodomain makes direct base contacts with the major groove of the double helix (and is thus known as the recognition helix), the amino-terminal arm makes contact in the minor groove, and there are extensive contacts with the sugar-phosphate backbone (Kissinger et al., 1990; Otting et al., 1990; Wohlberger et al., 1991).