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A dimeric viral SET domain methyltransferase specific to Lys27 of histone H3

Nature Structural & Molecular Biology volume 10, pages 187–196 (2003)Cite this article

Abstract

Site-specific lysine methylation of histones by SET domains is a hallmark for epigenetic control of gene transcription in eukaryotic organisms. Here we report that a SET domain protein from Paramecium bursaria chlorella virus can specifically di-methylate Lys27 in histone H3, a modification implicated in gene silencing. The solution structure of the viral SET domain reveals a butterfly-shaped head-to-head symmetric dimer different from other known protein methyltransferases. Each subunit consists of a Greek-key antiparallel β-barrel and a three-stranded open-faced sandwich that mediates the dimer interface. Cofactor S-adenosyl-L-methionine (SAM) binds at the opening of the β-barrel, and amino acids C-terminal to Lys27 in H3 and in the flexible C-terminal tail of the enzyme confer the specificity of this viral histone methyltransferase.

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Figure 1: Structure-based sequence alignment of SET domains.
Figure 2: Histone methyltransferase activity of vSET.
Figure 3: Structure determination of the vSET dimer.
Figure 4: Three-dimensional structure of the vSET dimer.
Figure 5: SAM and substrate recognition of vSET.
Figure 6: Mutational analysis of vSET.

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Acknowledgements

We thank J. Van Etten for providing the cDNA clone of PBCV-1 SET domain protein, and L. Chen and S. Mutjaba for technical advice. We are also grateful to A. Lustig (Biozentrum, University of Basel, Switzerland) for performing the analytic ultracentrifugation experiments. A.F. is a recipient of a Wellcome Trust Postdoctoral Fellowship. The work was supported by a grant from the National Institutes of Health to M.-M.Z.

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  1. Department of Physiology and Biophysics, Structural Biology Program, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, 10029, New York, USA

    Karishma L. Manzur, Amjad Farooq, Lei Zeng, Olga Plotnikova, Alexander W. Koch,  Sachchidanand & Ming-Ming Zhou

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Manzur, K., Farooq, A., Zeng, L. et al. A dimeric viral SET domain methyltransferase specific to Lys27 of histone H3. Nat Struct Mol Biol 10, 187–196 (2003). https://doi.org/10.1038/nsb898

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