The GyrA-box Determines the Geometry of DNA Bound to Gyrase and Couples DNA Binding to the Nucleotide Cycle

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2012 Sep 15

PMID 22977179

Citations 24

Authors

Martin A Lanz

Dagmar Klostermeier

Affiliations

Soon will be listed here.

Abstract

DNA gyrase catalyses the adenosine triphosphate-dependent introduction of negative supercoils into DNA. The enzyme binds a DNA-segment at the so-called DNA-gate and cleaves both DNA strands. DNA extending from the DNA-gate is bound at the perimeter of the cylindrical C-terminal domains (CTDs) of the GyrA subunit. The CTDs are believed to contribute to the wrapping of DNA around gyrase in a positive node as a prerequisite for strand passage towards negative supercoiling. A conserved seven amino acid sequence motif in the CTD, the so-called GyrA-box, has been identified as a hallmark feature of gyrases. Mutations of the GyrA-box abolish supercoiling. We show here that the GyrA-box marginally stabilizes the CTDs. Although it does not contribute to DNA binding, it is required for DNA bending and wrapping, and it determines the geometry of the bound DNA. Mutations of the GyrA-box abrogate a DNA-induced conformational change of the gyrase N-gate and uncouple DNA binding and adenosine triphosphate hydrolysis. Our results implicate the GyrA-box in coordinating DNA binding and the nucleotide cycle.

Citing Articles

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References

Costenaro L, Grossmann J, Ebel C, Maxwell A . Small-angle X-ray scattering reveals the solution structure of the full-length DNA gyrase a subunit. Structure. 2005; 13(2):287-96. DOI: 10.1016/j.str.2004.12.011. View

Gottler T, Klostermeier D . Dissection of the nucleotide cycle of B. subtilis DNA gyrase and its modulation by DNA. J Mol Biol. 2007; 367(5):1392-404. DOI: 10.1016/j.jmb.2007.01.055. View

Gubaev A, Hilbert M, Klostermeier D . The DNA-gate of Bacillus subtilis gyrase is predominantly in the closed conformation during the DNA supercoiling reaction. Proc Natl Acad Sci U S A. 2009; 106(32):13278-83. PMC: 2726392. DOI: 10.1073/pnas.0902493106. View

Tretter E, Berger J . Mechanisms for defining supercoiling set point of DNA gyrase orthologs: II. The shape of the GyrA subunit C-terminal domain (CTD) is not a sole determinant for controlling supercoiling efficiency. J Biol Chem. 2012; 287(22):18645-54. PMC: 3365746. DOI: 10.1074/jbc.M112.345736. View

Fu G, Wu J, Liu W, Zhu D, Hu Y, Deng J . Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigation. Nucleic Acids Res. 2009; 37(17):5908-16. PMC: 2761264. DOI: 10.1093/nar/gkp586. View

Reece R, Maxwell A . The C-terminal domain of the Escherichia coli DNA gyrase A subunit is a DNA-binding protein. Nucleic Acids Res. 1991; 19(7):1399-405. PMC: 333892. DOI: 10.1093/nar/19.7.1399. View

Ruthenburg A, Graybosch D, Huetsch J, Verdine G . A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias. J Biol Chem. 2005; 280(28):26177-84. DOI: 10.1074/jbc.M502838200. View

Arnold K, Bordoli L, Kopp J, Schwede T . The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics. 2005; 22(2):195-201. DOI: 10.1093/bioinformatics/bti770. View

Corbett K, Shultzaberger R, Berger J . The C-terminal domain of DNA gyrase A adopts a DNA-bending beta-pinwheel fold. Proc Natl Acad Sci U S A. 2004; 101(19):7293-8. PMC: 409912. DOI: 10.1073/pnas.0401595101. View

10.

Morais Cabral J, Jackson A, Smith C, Shikotra N, Maxwell A, Liddington R . Crystal structure of the breakage-reunion domain of DNA gyrase. Nature. 1997; 388(6645):903-6. DOI: 10.1038/42294. View

11.

Roca J . The path of the DNA along the dimer interface of topoisomerase II. J Biol Chem. 2004; 279(24):25783-8. DOI: 10.1074/jbc.M402555200. View

12.

Heddle J, Mitelheiser S, Maxwell A, Thomson N . Nucleotide binding to DNA gyrase causes loss of DNA wrap. J Mol Biol. 2004; 337(3):597-610. DOI: 10.1016/j.jmb.2004.01.049. View

13.

Tretter E, Berger J . Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A nonconserved acidic C-terminal tail modulates Escherichia coli gyrase activity. J Biol Chem. 2012; 287(22):18636-44. PMC: 3365713. DOI: 10.1074/jbc.M112.345678. View

14.

Lanz M, Klostermeier D . Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains defines an early step in the supercoiling cycle. Nucleic Acids Res. 2011; 39(22):9681-94. PMC: 3239214. DOI: 10.1093/nar/gkr680. View

15.

Roca J, Berger J, Harrison S, Wang J . DNA transport by a type II topoisomerase: direct evidence for a two-gate mechanism. Proc Natl Acad Sci U S A. 1996; 93(9):4057-62. PMC: 39486. DOI: 10.1073/pnas.93.9.4057. View

16.

Vos S, Tretter E, Schmidt B, Berger J . All tangled up: how cells direct, manage and exploit topoisomerase function. Nat Rev Mol Cell Biol. 2011; 12(12):827-41. PMC: 4351964. DOI: 10.1038/nrm3228. View

17.

Bates A, ODea M, Gellert M . Energy coupling in Escherichia coli DNA gyrase: the relationship between nucleotide binding, strand passage, and DNA supercoiling. Biochemistry. 1996; 35(5):1408-16. DOI: 10.1021/bi952433y. View

18.

Kampranis S, Maxwell A . Conversion of DNA gyrase into a conventional type II topoisomerase. Proc Natl Acad Sci U S A. 1996; 93(25):14416-21. PMC: 26147. DOI: 10.1073/pnas.93.25.14416. View

19.

Liu L, Wang J . DNA-DNA gyrase complex: the wrapping of the DNA duplex outside the enzyme. Cell. 1978; 15(3):979-84. DOI: 10.1016/0092-8674(78)90281-7. View

20.

Hsieh T, Yen T, Lin T, Chang H, Huang S, Hsu C . Twisting of the DNA-binding surface by a beta-strand-bearing proline modulates DNA gyrase activity. Nucleic Acids Res. 2010; 38(12):4173-81. PMC: 2896533. DOI: 10.1093/nar/gkq153. View