Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of, Baker Center for Bioinformatics and Biological Statistics

Document Type

Article

Publication Version

Published Version

Publication Date

3-12-2004

Journal or Book Title

Journal of Molecular Biology

Volume

337

Issue

1

First Page

65

Last Page

76

DOI

10.1016/j.jmb.2004.01.011

Abstract

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.

Comments

This article is published as Tolstorukov, Michael Y., Robert L. Jernigan, and Victor B. Zhurkin. "Protein–DNA hydrophobic recognition in the minor groove is facilitated by sugar switching." Journal of molecular biology 337, no. 1 (2004): 65-76. doi: 10.1016/j.jmb.2004.01.011. Posted with permission.

Rights

Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.

Language

en

File Format

application/pdf

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