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Molecular architecture of a eukaryotic DNA transposase

Nature Structural & Molecular Biology volume 12, pages 715–721 (2005)Cite this article

Abstract

Mobile elements and their inactive remnants account for large proportions of most eukaryotic genomes, where they have had central roles in genome evolution. Over 50 years ago, McClintock reported a form of stress-induced genome instability in maize in which discrete DNA segments move between chromosomal locations. Our current mechanistic understanding of enzymes catalyzing transposition is largely limited to prokaryotic transposases. The Hermes transposon from the housefly is part of the eukaryotic hAT superfamily that includes hobo from Drosophila, McClintock's maize Activator and Tam3 from snapdragon. We report here the three-dimensional structure of a functionally active form of the transposase from Hermes at 2.1-Å resolution. The Hermes protein has some structural features of prokaryotic transposases, including a domain with a retroviral integrase fold. However, this domain is disrupted by the insertion of an additional domain. Finally, transposition is observed only when Hermes assembles into a hexamer.

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Figure 1: Structure of Hermes79–612.
Figure 2: Hermes79–61g dimerizes through domain swapping.
Figure 3: The hexameric form of Hermes79–612.
Figure 4: Schematic of the mechanism of Hermes transposition.

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Acknowledgements

We thank M. Gellert, S. Vasudevan and D. Ronning for helpful discussions and comments on the manuscript. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Basic Energy Sciences, Office of Science, under contract no. W-31-109-Eng-38. This study used the high-performance computational capabilities of the Helix Systems at the National Institutes of Health, Bethesda, MD (http://helix.nih.gov). N.L.C. is an Investigator of the Howard Hughes Medical Institute.

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Author notes

  1. Primrose Musingarimi

    Present address: Department of Social Policy, London School of Economics and Political Science, London, WC2A 2AE, UK

Authors and Affiliations

  1. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Alison B Hickman, Zhanita N Perez, Primrose Musingarimi, Rodolfo Ghirlando & Fred Dyda

  2. Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, 21205, Maryland, USA

    Liqin Zhou & Nancy L Craig

  3. Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Jenny E Hinshaw

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Correspondence to Fred Dyda.

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Supplementary information

Supplementary Fig. 1

Electron density maps of Hermes 70–612. (PDF 11787 kb)

Supplementary Fig. 2

DNA binding by Hermes, assessed by co-elution during size exclusion chromatography, requires the 79–150 domain. (PDF 1206 kb)

Supplementary Fig. 3

Sedimentation equilibrium profiles for heterotetrameric (D1) and hexameric (H) Hermes 79–612. (PDF 2439 kb)

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Hickman, A., Perez, Z., Zhou, L. et al. Molecular architecture of a eukaryotic DNA transposase. Nat Struct Mol Biol 12, 715–721 (2005). https://doi.org/10.1038/nsmb970

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