Structure of an atypical Tudor domain in the Drosophila Polycomblike protein

Protein Sci. 2010 Oct;19(10):1906-16. doi: 10.1002/pro.476.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites / genetics
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Lysine / analogs & derivatives
  • Lysine / chemistry
  • Lysine / metabolism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Solutions

Substances

  • Drosophila Proteins
  • Ligands
  • Pcl protein, Drosophila
  • Recombinant Proteins
  • Repressor Proteins
  • Solutions
  • 2-methyllysine
  • Lysine

Associated data

  • PDB/2XK0