STRUCTURE OF THE EVEN-SKIPPED HOMEODOMAIN COMPLEXED TO AT-RICH DNA - NEW PERSPECTIVES ON HOMEODOMAIN SPECIFICITY

even-skipped is a homeobox gene important in controlling segment patte rning in the embryonic fruit fly. Its homeobox encodes a DNA binding d omain which binds with similar affinities to two DNA consensus sequenc es, one AT-rich, the other GC-rich. We describe a crystallographic ana lysis of the Even-skipped homeodomain complexed to an AT-rich oligonuc leotide at 2.0 Angstrom resolution, The structure reveals a novel arra ngement of two homeodomains bound to one 10 bp DNA sequence in a tande m fashion. This arrangement suggests a mechanism for the homeoproteins ' regulatory specificity, In addition, the functionally important resi due Gln50 is observed in multiple conformations making direct and wate r-mediated hydrogen bonds with the DNA bases.