Crystal structure of a MAT alpha 2 homeodomain-operator complex suggests a general model for homeodomain-DNA interactions.
The MAT alpha 2 homeodomain regulates the expression of cell type-specific genes in yeast. We have determined the 2.7 A resolution crystal structure of the alpha 2 homeodomain bound to a biologically relevant DNA sequence. The DNA in this complex is contacted primarily by the third of three alpha-helices, with additional contacts coming from an N-terminal arm. Comparison of the yeast alpha 2 and the Drosophila engrailed homeodomain-DNA complexes shows that the protein fold is highly conserved, despite a 3-residue insertion in alpha 2 and only 27% sequence identity between the two homeodomains. Moreover, the orientation of the recognition helix on the DNA is also conserved. This docking arrangement is maintained by side chain contacts with the DNA--primarily the sugar-phosphate backbone--that are identical in alpha 2 and engrailed. Since these residues are conserved among all homeodomains, we propose that the contacts with the DNA are also conserved and suggest a general model for homeodomain-DNA interactions.
Wolberger
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Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185.
Vershon
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Liu
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Johnson
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Pabo
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CO
D001483:Base Sequence; D003461:Crystallography; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D005801:Genes, Homeobox; D000072235:Mating Factor; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D009875:Operator Regions, Genetic; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D016415:Sequence Alignment; D014961:X-Ray Diffraction
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009841:Oligonucleotides; D010455:Peptides; D000072235:Mating Factor