Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites
Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Amino Acid Sequence; Animals; Bacteria; Base Sequence; DNA; Drosophila Proteins; Drosophila melanogaster; Genome, Insect; Homeodomain Proteins; Humans; Models, Molecular; Phylogeny; Protein Engineering; Protein Structure, Tertiary; Two-Hybrid System Techniques
Life Sciences | Medicine and Health Sciences
We describe the comprehensive characterization of homeodomain DNA-binding specificities from a metazoan genome. The analysis of all 84 independent homeodomains from D. melanogaster reveals the breadth of DNA sequences that can be specified by this recognition motif. The majority of these factors can be organized into 11 different specificity groups, where the preferred recognition sequence between these groups can differ at up to four of the six core recognition positions. Analysis of the recognition motifs within these groups led to a catalog of common specificity determinants that may cooperate or compete to define the binding site preference. With these recognition principles, a homeodomain can be reengineered to create factors where its specificity is altered at the majority of recognition positions. This resource also allows prediction of homeodomain specificities from other organisms, which is demonstrated by the prediction and analysis of human homeodomain specificities.
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Citation: Cell. 2008 Jun 27;133(7):1277-89. Link to article on publisher's site