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Structural basis for gate-DNA recognition and bending by type IIA topoisomerases

Nature volume 450, pages 1201–1205 (2007)Cite this article

Abstract

Type II topoisomerases disentangle DNA to facilitate chromosome segregation, and represent a major class of therapeutic targets. Although these enzymes have been studied extensively, a molecular understanding of DNA binding has been lacking. Here we present the structure of a complex between the DNA-binding and cleavage core of Saccharomyces cerevisiae Topo II (also known as Top2) and a gate-DNA segment. The structure reveals that the enzyme enforces a 150° DNA bend through a mechanism similar to that of remodelling proteins such as integration host factor. Large protein conformational changes accompany DNA deformation, creating a bipartite catalytic site that positions the DNA backbone near a reactive tyrosine and a coordinated magnesium ion. This configuration closely resembles the catalytic site of type IA topoisomerases, reinforcing an evolutionary link between these structurally and functionally distinct enzymes. Binding of DNA facilitates opening of an enzyme dimerization interface, providing visual evidence for a key step in DNA transport.

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Figure 1: Structure of the Topo II DNA-binding and cleavage core bound to DNA.
Figure 2: Topo II severely bends DNA.
Figure 3: Topo II conformational changes accompany DNA binding.
Figure 4: Close up of the Topo II active site.

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Protein Data Bank

Data deposits

Coordinates have been deposited in the RSCB PDB under the accession number 2RGR.

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Acknowledgements

The authors are grateful to D. Herschlag for advice on the choice of DNA substrate, and to members of the Berger laboratory for discussions. This work was supported by a NIH Training Grant position to K.C.D. and by the NCI.

Author Contributions K.C.D. and J.M.B. designed the experimental plan, analysed the data, and wrote the paper. K.C.D. performed the research.

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Authors and Affiliations

  1. Department of Chemistry, Chemical Biology Graduate Program, College of Chemistry, University of California, Berkeley, California 94720-3220, USA,

    Ken C. Dong

  2. Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, QB3 Institute, Stanley Hall 3220, University of California at Berkeley, Berkeley, California 94720-3220, USA,

    Ken C. Dong & James M. Berger

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  1. Ken C. Dong
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Correspondence to James M. Berger.

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Supplementary Information

The file contains Supplementary Table 1 and Supplementary Figures S1-S9 with Legends, Legend to Supplementary Movie 1 and additional references. (PDF 12278 kb)

Supplementary Movie 1

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Dong, K., Berger, J. Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450, 1201–1205 (2007). https://doi.org/10.1038/nature06396

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