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Structures of ParB bound to DNA reveal mechanism of partition complex formation

Nature volume 438, pages 516–519 (2005)Cite this article

Abstract

The faithful inheritance of genetic information, which is essential for all organisms, requires accurate DNA partition (segregation) at cell division. In prokaryotes, partition is mediated by par systems, for which the P1 plasmid system of Escherichia coli is a prototype comprising a partition site and two proteins, ParA and ParB1,2. To form the partition complex necessary for segregation, P1 ParB must recognize a complicated arrangement of A-box and B-box DNA motifs located on opposite ends of a sharply bent parS partition site of ∼74 bp (refs 3–7). Here we describe structures of ParB bound to partition sites. ParB forms an asymmetric dimer with extended amino-terminal HTH (helix–turn–helix) domains that contact A-boxes. The two HTH domains emanate from a dimerized DNA-binding module composed of a six-stranded β-sheet coiled-coil that binds B-boxes. Strikingly, these individual DNA-binding modules rotate freely about a flexible linker, enabling them to contact several arrangements of A- and B-boxes. Most notably, each DNA-binding element binds to and thus bridges adjacent DNA duplexes. These unique structural features of ParB explain how this protein can bind complex arrays of A- and B-box elements on adjacent DNA arms of the looped partition site.

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Figure 1: Overall structure of the ParB–parS-small complex.
Figure 2: ParB dimer flexibility and asymmetry.
Figure 3: P1 ParB is a DNA-bridging factor.
Figure 4: ParB interactions with A- and B-box motifs.

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Acknowledgements

We thank Advanced Light Source and their support staff, with special thanks to C. Ralston. The ALS is supported by the Director, Office of Science, Office of Basic Energy Sciences, Materials Sciences Division, of the US Department of Energy at the Lawrence Berkeley National Laboratory. This work was supported by a Burroughs Wellcome Career Development Award (to M.A.S.) and a grant from the Canadian Institutes of Health Research (to B.E.F.).

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Author notes

  1. Maria A. Schumacher

    Present address: M. D. Anderson Cancer Center, Department of Biochemistry & Molecular Biology, Unit 1000, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Oregon, 97239-3098, Portland, USA

    Maria A. Schumacher

  2. Science University,

    Maria A. Schumacher

  3. Department of Molecular and Medical Genetics, University of Toronto, Ontario, M5S 1A8, Toronto, Canada

    Barbara E. Funnell

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Correspondence to Maria A. Schumacher.

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The X-ray crystallographic coordinates and structure factor files have been deposited with the Protein Data Bank under accession code 1ZX4. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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This file contains the Supplementary Data, Supplementary Methods, Supplementary Figures 1–3 and Supplementary Table 1. (DOC 1587 kb)

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Schumacher, M., Funnell, B. Structures of ParB bound to DNA reveal mechanism of partition complex formation. Nature 438, 516–519 (2005). https://doi.org/10.1038/nature04149

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