Crystal structure of the Msx-1 homeodomain/DNA complex

The Msx-1 homeodomain protein plays a crucial role in craniofacial, limb, a nd nervous system development. Homeodomain DNA-binding domains are comprise d of 60 amino acids that show a high degree of evolutionary conservation. W e have determined the structure of the Msx-1 homeodomain complexed to DNA a t 2.2 Angstrom resolution. The structure has an unusually well-ordered N-te rminal arm with a unique trajectory across the minor groove of the DNA. DNA specificity conferred by bases flanking the core TAAT sequence is explaine d by well ordered water-mediated interactions at Q50. Most interactions see n at the TAAT sequence are typical of the interactions seen in other homeod omain structures. Comparison of the Msx-1-HD structure to all other high re solution HD-DNA complex structures indicate a remarkably well-conserved sph ere of hydration between the DNA and protein in these complexes.