title: Structure of an atypical Tudor domain in the Drosophila Polycomblike protein.
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.
authors.affiliation: Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, Neuherberg, Germany.
authors.forename: Anders
authors.initials: A
authors.lastname: Friberg
authors.forename: Anna
authors.initials: A
authors.lastname: Oddone
authors.forename: Tetyana
authors.initials: T
authors.lastname: Klymenko
authors.forename: Jürg
authors.initials: J
authors.lastname: Müller
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012996:Solutions
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; C095065:Pcl protein, Drosophila; D011994:Recombinant Proteins; D012097:Repressor Proteins; D012996:Solutions; C049907:2-methyllysine; D008239:Lysine