Definitive role of polar residue clusters in B-DNA major groove recognition by protein factors

Abstract

The 3D structural data for a number of protein-DNA complexes were used to analyze the regions of specific contact with the major groove of B-DNA double helix. The set included seven nonhomologous complexes featuring 12 DNA-binding domains of transcription factors and regulatory factors. The protein domains differed in structure, contained different motifs in the binding region, and broadly varied in chain length, from 30 to 200 residues. Protein-DNA interaction was assessed as hydrogen bonding between polar atoms and van der Waals contacts between nonpolar atoms. The binding sites were formed mainly through polar side chain interactions. On average, the recognition site comprises seven residues, six of them polar. The contact residues nearly always belong to a largest polar cluster of the protein. Thus one can think that the protein polar residue clusters play an important role in forming the protein-DNA recognition module.