DNA minor groove sensing and widening by the CCAAT-binding complex.
The CCAAT box is a frequent element of eukaryotic promoters, and its specific recognition by the conserved heterotrimeric CCAAT-binding complex (CBC) constitutes a key step in promoter organization and regulation of transcription. Here, we report the crystal structures of the CBC from Aspergillus nidulans in the absence and in complex with double-stranded DNA at 1.8 Å resolution. The histone-like subunits HapC and HapE induce nucleosome-like DNA bending by interacting with the sugar-phosphate backbone. Minor groove sensing and widening by subunit HapB tightly anchor the CBC to the CCAAT box, as shown by structural and biochemical data. Furthermore, crucial interactions of the DNA duplex with subunit HapB provide an explanation for the sequence specificity of the CBC. The herein-described mode of transcription factor binding answers the question of how histone proteins gained sequence specificity for the CCAAT box.
Center for Integrated Protein Science, Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Garching 85747, Germany.
Eva M
EM
Huber
Daniel H
DH
Scharf
Peter
P
Hortschansky
Michael
M
Groll
Axel A
AA
Brakhage
D001233:Aspergillus nidulans; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004271:DNA, Fungal / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry*; D015966:Gene Expression Regulation, Fungal; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D023081:CCAAT-Binding Factor; D004271:DNA, Fungal; D005656:Fungal Proteins; C100785:HapC protein, Emericella nidulans; C111072:aab-1 protein, Neurospora