Structure-based Subfamily Classification of Homeodomains

Eukaryotic DNA-binding proteins mediate many important steps in embryonic development and gene regulation. Consequently, a better understanding of these proteins would hopefully allow a more complete picture of gene regulation to be determined. In this study, a structure-based subfamily classification of the homeodomain family of DNA-binding proteins was undertaken in order to determine whether sub-groupings of a protein family could be identified that corresponded to differences in specific function, and identification of subfamily-determining residues was performed in order to gain some insight on functional differences via analysis of the residue properties. Subfamilies appear to have different specific DNA binding properties, according to DNA profiles obtained from TRANSFAC [1] and other sources in the literature. Subfamily-specific residues appear to be frequently associated with the protein-DNA interface and may influence DNA binding via interactions with the DNA phosphate backbone; these residues form a conserved profile uniquely identifying each subfamily.MAS