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. 2002 Apr 1;30(7):1704-11.
doi: 10.1093/nar/30.7.1704.

Structural analysis of conserved base pairs in protein-DNA complexes

Leonid A Mirny  1 , Mikhail S Gelfand
Affiliations

Structural analysis of conserved base pairs in protein-DNA complexes

Leonid A Mirny et al. Nucleic Acids Res. .

Abstract

Understanding of protein-DNA interactions is crucial for prediction of DNA-binding specificity of transcription factors and design of novel DNA-binding proteins. In this paper we develop a novel approach to analysis of protein-DNA interactions. We bring together two sources of information: (i) structures of protein-DNA complexes (PDB/NDB database) and (ii) experimentally obtained sites recognized by DNA-binding proteins. Sites are used to compute conservation (information content) of each base pair, which indicates relative importance of the base pair in specific recognition. The main result of this study is that conservation of base pairs in a site exhibits significant correlation with the number of contacts the base pairs have with the protein. In particular, base pairs that have more contacts with the protein are more conserved in evolution. As natural as it is, this result has never been reported before. We also observe that for most of the studied proteins, hydrogen bonds and hydrophobic interactions alone cannot explain the pattern of evolutionary conservation in the binding site suggesting cumulative contribution of different types of interactions to specific recognition. Implications for prediction of the DNA-binding specificity are discussed.

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Figures

Figure 1
Figure 1
Crp site. (Top) Thin line shows the number of interactions n base pairs have with the protein. The number of hydrogen bonds formed by a base pair (including water-mediated bonds) is shown by large circles. The number of hydrophobic interactions between a base pair and the protein is shown by squares. (Bottom) Variability (entropy) in the footprinted DNA sites. The ‘consensus’ (most frequent) nucleotides are shown by letters above the plot. The color of a letter indicates its conservation from blue (conserved) to red (variable).
Figure 2
Figure 2
PurR site; notation as in Figure 1.
Figure 3
Figure 3
Ihf site; notation as in Figure 1.
Figure 4
Figure 4
Trp site; notation as in Figure 1.
See this image and copyright information in PMC

References

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