title: The solution structure of the native K50 Bicoid homeodomain bound to the consensus TAATCC DNA-binding site.
abstract: The solution structure of the homeodomain of the Drosophila morphogenic protein Bicoid (Bcd) complexed with a TAATCC DNA site is described. Bicoid is the only known protein that uses a homeodomain to regulate translation, as well as transcription, by binding to both RNA and DNA during early Drosophila development; in addition, the Bcd homeodomain can recognize an array of different DNA sites. The dual functionality and broad recognition capabilities signify that the Bcd homeodomain may possess unique structural/dynamic properties. Bicoid is the founding member of the K50 class of homeodomain proteins, containing a lysine residue at the critical 50th position (K50) of the homeodomain sequence, a residue required for DNA and RNA recognition; Bcd also has an arginine residue at the 54th position (R54), which is essential for RNA recognition. Bcd is the only known homeodomain with the K50/R54 combination of residues. The Bcd structure indicates that this homeodomain conforms to the conserved topology of the homeodomain motif, but exhibits a significant variation from other homeodomain structures at the end of helix 1. A key result is the observation that the side-chains of the DNA-contacting residues K50, N51 and R54 all show strong signs of flexibility in the protein-DNA interface. This finding is supportive of the adaptive-recognition theory of protein-DNA interactions.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Medical Sciences Building, Cincinnati, OH 45267-0524, USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Baird-Titus
authors.forename: Kimber
authors.initials: K
authors.lastname: Clark-Baldwin
authors.forename: Vrushank
authors.initials: V
authors.lastname: Dave
authors.forename: Carol A
authors.initials: CA
authors.lastname: Caperelli
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Mark
authors.initials: M
authors.lastname: Rance
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000502:physiology*; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D046911:Macromolecular Substances; D012097:Repressor Proteins; D015534:Trans-Activators; C056478:bcd protein, Drosophila; D004247:DNA