Structure of the even-skipped homeodomain complexed to AT-rich DNA: new perspectives on homeodomain specificity.
even-skipped is a homeobox gene important in controlling segment patterning in the embryonic fruit fly. Its homeobox encodes a DNA binding domain which binds with similar affinities to two DNA consensus sequences, one AT-rich, the other GC-rich. We describe a crystallographic analysis of the Even-skipped homeodomain complexed to an AT-rich oligonucleotide at 2.0 A resolution. The structure reveals a novel arrangement of two homeodomains bound to one 10 bp DNA sequence in a tandem fashion. This arrangement suggests a mechanism for the homeoproteins' regulatory specificity. In addition, the functionally important residue Gln50 is observed in multiple conformations making direct and water-mediated hydrogen bonds with the DNA bases.
Hirsch
J A
JA
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Aggarwal
A K
AK
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000737:chemistry / Q000196:embryology / Q000235:genetics*; D004563:Electrochemistry; D005801:Genes, Homeobox; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011487:Protein Conformation; D012997:Solvents; D014157:Transcription Factors
D001426:Bacterial Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D012997:Solvents; D014157:Transcription Factors; C052837:eve protein, Drosophila; D004247:DNA