Editing Homeobox (section)

===Sequence specificity===

Homeodomains can bind both specifically and nonspecifically to [[B-DNA]] with the C-terminal recognition helix aligning in the DNA's major groove and the unstructured peptide "tail" at the N-terminus aligning in the minor groove. The recognition helix and the inter-helix loops are rich in [[arginine]] and [[lysine]] residues, which form [[hydrogen bond]]s to the DNA backbone. [[conservation (genetics)|Conserved]] [[hydrophobic]] residues in the center of the recognition helix aid in stabilizing the helix packing. Homeodomain proteins show a preference for the DNA sequence 5'-TAAT-3'; sequence-independent binding occurs with significantly lower affinity. The specificity of a single homeodomain protein is usually not enough to recognize specific target gene promoters, making cofactor binding an important mechanism for controlling binding sequence specificity and target gene expression. To achieve higher target specificity, homeodomain proteins form complexes with other transcription factors to recognize the [[promoter (biology)|promoter region]] of a specific target gene.