homeodomains

Homeodomains are DNA-binding protein domains of about 60 amino acids found in a broad family of transcription factors that regulate development in animals, plants, and fungi. They are encoded by homeobox genes, which contain a conserved 180-base-pair sequence called the homeobox that encodes the homeodomain.

Structure and DNA binding: The homeodomain adopts a helix-turn-helix fold composed of three alpha helices. Helix 3 recognizes DNA, inserting major-groove contacts into a recognition motif. A conserved sequence, including the motif WFQNRR in helix 3, supports DNA contact, and the proteins typically bind to TAAT-containing core motifs, with binding specificity influenced by flanking sequences and cofactors.

Evolution and diversity: Homeobox genes form large families; in animals they include HOX clusters that pattern the anterior-posterior axis; in plants there are homeobox families such as KNOX and HD-ZIP; the structure is highly conserved but regulatory contexts differ.

Function and mechanism: They are often components of larger transcription factors; they act as master regulators during embryonic development and organ formation, controlling target gene expression; cofactors such as PBC and MEIS families and other proteins modulate DNA-binding specificity.

Significance: Mutations or misexpression can lead to developmental defects and homeotic transformations; studying homeodomains informs understanding of gene regulation and evolutionary change.