Protein-DNA hydrophobic recognition in the minor groove is facilitated by sugar switching

J Mol Biol. 2004 Mar 12;337(1):65-76. doi: 10.1016/j.jmb.2004.01.011.


Information readout in the DNA minor groove is accompanied by substantial DNA deformations, such as sugar switching between the two conformational domains, B-like C2'-endo and A-like C3'-endo. The effect of sugar puckering on the sequence-dependent protein-DNA interactions has not been studied systematically, however. Here, we analyzed the structural role of A-like nucleotides in 156 protein-DNA complexes solved by X-ray crystallography and NMR. To this end, a new algorithm was developed to distinguish interactions in the minor groove from those in the major groove, and to calculate the solvent-accessible surface areas in each groove separately. Based on this approach, we found a striking difference between the sets of amino acids interacting with B-like and A-like nucleotides in the minor groove. Polar amino acids mostly interact with B-nucleotides, while hydrophobic amino acids interact extensively with A-nucleotides (a hydrophobicity-structure correlation). This tendency is consistent with the larger exposure of hydrophobic surfaces in the case of A-like sugars. Overall, the A-like nucleotides aid in achieving protein-induced fit in two major ways. First, hydrophobic clusters formed by several consecutive A-like sugars interact cooperatively with the non-polar surfaces in proteins. Second, the sugar switching occurs in large kinks promoted by direct protein contact, predominantly at the pyrimidine-purine dimeric steps. The sequence preference for the B-to-A sugar repuckering, observed for pyrimidines, suggests that the described DNA deformations contribute to specificity of the protein-DNA recognition in the minor groove.

MeSH terms

  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation*
  • Oligodeoxyribonucleotides / chemistry*
  • Oligodeoxyribonucleotides / metabolism
  • Protein Conformation


  • DNA-Binding Proteins
  • Oligodeoxyribonucleotides
  • DNA