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Structure of the bacteriophage T4 DNA adenine methyltransferase

Nature Structural & Molecular Biology volume 10, pages 849–855 (2003)Cite this article

Abstract

DNA-adenine methylation at certain GATC sites plays a pivotal role in bacterial and phage gene expression as well as bacterial virulence. We report here the crystal structures of the bacteriophage T4Dam DNA adenine methyltransferase (MTase) in a binary complex with the methyl-donor product S-adenosyl-L-homocysteine (AdoHcy) and in a ternary complex with a synthetic 12-bp DNA duplex and AdoHcy. T4Dam contains two domains: a seven-stranded catalytic domain that harbors the binding site for AdoHcy and a DNA binding domain consisting of a five-helix bundle and a β-hairpin that is conserved in the family of GATC-related MTase orthologs. Unexpectedly, the sequence-specific T4Dam bound to DNA in a nonspecific mode that contained two Dam monomers per synthetic duplex, even though the DNA contains a single GATC site. The ternary structure provides a rare snapshot of an enzyme poised for linear diffusion along the DNA.

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Figure 1: Structure-based sequence alignment of the selected Dam MTase orthologs.
Figure 2: The binary structure of T4Dam–AdoHcy.
Figure 3: The loose ternary structure of T4Dam–DNA–AdoHcy.

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Acknowledgements

We thank beamline staff for help with X-ray data collection at beamlines X12C, X25 and X26C in the facilities of the National Synchrotron Light Source, Brookhaven National Laboratory, R.M. Blumenthal (Medical College of Ohio) for comments and M. Churchill (University of Colorado) for discussion. These studies were supported in part by US Public Health Services grants to S.H and X.C. and the Georgia Research Alliance.

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Author notes

  1. Valeri Kossykh

    Present address: Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, 77555, Texas, USA

  2. Lan Zhou

    Present address: Office of Information Technology, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA

Authors and Affiliations

  1. Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, 30322, Georgia, USA

    Zhe Yang, John R Horton, Lan Zhou, Xu Jia Zhang, Aiping Dong, Xing Zhang & Xiaodong Cheng

  2. Department of Biology, University of Rochester, Rochester, 14627-0211, New York, USA

    Samuel L Schlagman, Valeri Kossykh & Stanley Hattman

  3. Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Xu Jia Zhang

  4. Department of Biochemistry, University of Toronto, Toronto, M5S1A8, Ontario, Canada

    Aiping Dong

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  1. Zhe Yang
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Correspondence to Xiaodong Cheng.

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Yang, Z., Horton, J., Zhou, L. et al. Structure of the bacteriophage T4 DNA adenine methyltransferase. Nat Struct Mol Biol 10, 849–855 (2003). https://doi.org/10.1038/nsb973

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