Structure of an atypical Tudor domain in the Drosophila Polycomblike protein

Authors

  • Anders Friberg,

    1. Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
    2. Department Chemie, Munich Center for Integrated Protein Science at Chair of Biomolecular NMR, Technische Universität München, Lichtenbergstr. 4, 85747 Garching
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    • Anders Friberg and Anna Oddone contributed equally to this work.

  • Anna Oddone,

    1. European Molecular Biology Laboratory (EMBL), Meyerhofstr. 1, 69117 Heidelberg, Germany
    2. Centre for Genomic Regulation (CRG), Doctor Aiguader 88, 08003 Barcelona, Spain
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    • Anders Friberg and Anna Oddone contributed equally to this work.

  • Tetyana Klymenko,

    1. European Molecular Biology Laboratory (EMBL), Meyerhofstr. 1, 69117 Heidelberg, Germany
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  • Jürg Müller,

    1. European Molecular Biology Laboratory (EMBL), Meyerhofstr. 1, 69117 Heidelberg, Germany
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  • Michael Sattler

    Corresponding author
    1. Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
    2. Department Chemie, Munich Center for Integrated Protein Science at Chair of Biomolecular NMR, Technische Universität München, Lichtenbergstr. 4, 85747 Garching
    • Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

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Abstract

Post-translational modifications of histone tails are among the most prominent epigenetic marks and play a critical role in transcriptional control at the level of chromatin. The Polycomblike (Pcl) protein is part of a histone methyltransferase complex (Pcl-PRC2) responsible for high levels of histone H3 K27 trimethylation. Studies in Drosophila larvae suggest that Pcl is required for anchoring Pcl-PRC2 at target genes, but how this is achieved is unknown. Pcl comprises a Tudor domain and two PHD fingers. These domains are known to recognize methylated lysine or arginine residues and could contribute to targeting of Pcl-PRC2. Here, we report an NMR structure of the Tudor domain from Drosophila Pcl (Pcl-Tudor) and binding studies with putative ligands. Pcl-Tudor contains an atypical, incomplete aromatic cage that does not interact with known Tudor domain ligands, such as methylated lysines or arginines. Interestingly, human Pcl orthologs exhibit a complete aromatic cage, suggesting that they may recognize methylated lysines. Structural comparison with other Tudor domains suggests that Pcl-Tudor may engage in intra- or intermolecular interactions through an exposed hydrophobic surface patch.

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