Insights into nonspecific binding of homeodomains from a structure of MATα2 bound to DNA

Abstract
The 2.1-Å resolution crystal structure of the MATα2 homeodomain bound to DNA reveals the unexpected presence of two nonspecifically bound α2 homeodomains, in addition to the two α2 homeodomains bound to canonical α2 binding sites. One of the extra homeodomains makes few base-specific contacts, while the other extra homeodomain binds to DNA in a previously unobserved manner. This unusually bound homeodomain is rotated on the DNA, making possible major groove contacts by side-chains that normally do not contact the DNA. This alternate docking may represent one way in which homeodomains sample nonspecific DNA sequences. Proteins 2003;51:544–551.