CRYSTAL-STRUCTURE OF A PAIRED DOMAIN-DNA COMPLEX AT 2.5-ANGSTROM RESOLUTION REVEALS STRUCTURAL BASIS FOR PAX DEVELOPMENTAL MUTATIONS

The 2.5 Angstrom resolution structure of a cocrystal containing the pa ired domain from the Drosophila paired (prd) protein and a 15 bp site shows structually independent N-terminal and C-terminal subdomains. Ea ch of these domains contains a helical region resembling the homeodoma in and the Hin recombinase. The N-terminal domain makes extensive DNA contacts, using a novel beta turn motif that binds in the minor groove and a helix-turn-helix unit with a docking arrangement surprisingly s imilar to that of the lambda repressor. The C-terminal domain is not e ssential for prd binding and does not contact the optimized site. All known developmental missense mutations in the paired box of mammalian Pax genes map to the N-terminal subdomain, and most of them are found at the protein-DNA interface.