International
Tables for
Crystallography
Volume F
Crystallography of biological macromolecules
Edited by M. G. Rossmann and E. Arnold

International Tables for Crystallography (2006). Vol. F. ch. 23.2, p. 583   | 1 | 2 |

Section 23.2.4.2. Single-stranded sequence-nonspecific DNA–protein interactions

A. E. Hodela and F. A. Quiochob

aDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA, and  bHoward Hughes Medical Institute and Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA

23.2.4.2. Single-stranded sequence-nonspecific DNA–protein interactions

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There have been a few reports of single-stranded DNA–protein complex structures, all of which involve the sequence-nonspecific recognition of DNA. In the binding of a tetranucleotide to the exonuclease active site of the DNA polymerase I Klenow fragment (Freemont et al., 1988[link]), extensive hydrogen-bonding interactions between the sugar–phosphate backbone and the protein are observed. This provides the most intuitive mechanism for sequence-nonspecific nucleic acid binding, where the protein simply recognizes the phosphate backbone of a single-stranded coil. The protein also appears to form a few hydrophobic interactions with the DNA bases; however, these interactions, which include the partial intercalation between two bases, are thought to be nonspecific.

The structure of replication protein A complexed with single-stranded DNA does not exhibit the intuitive nonspecific mechanism of recognition found in the Klenow fragment (Bochkarev et al., 1997[link]). In this structure, the DNA is extended with its bases splayed out over the surface of the protein. The bases form several pairwise stacking interactions that are interrupted by intercalating protein side chains. Contrary to the sequence-nonspecific nature of recognition, numerous hydrogen bonds are found between the protein and the bases of the DNA strand. These base-dependent contacts require that the protein–DNA interactions must be flexible and plastic in order to accommodate different base sequences.

References

First citation Bochkarev, A., Pfuetzner, R. A., Edwards, A. M. & Frappier, L. (1997). Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA. Nature (London), 385, 176–181.Google Scholar
First citation Freemont, P. S., Friedman, J. M., Beese, L. S., Sanderson, M. R. & Steitz, T. A. (1988). Cocrystal structure of an editing complex of Klenow fragment with DNA. Proc. Natl Acad. Sci. USA, 85, 8924–8928.Google Scholar








































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