Structure of an atypical Tudor domain in the Drosophila Polycomblike protein

被引:16
作者
Friberg, Anders [1 ,2 ]
Oddone, Anna [3 ,4 ]
Klymenko, Tetyana [3 ]
Mueller, Juerg [3 ]
Sattler, Michael [1 ,2 ]
机构
[1] Helmholtz Zentrum Munchen, Inst Biol Struct, D-85764 Neuherberg, Germany
[2] Tech Univ Munich, Dept Chem, Munich Ctr Integrated Prot Sci, Chair Biomol NMR, D-85747 Garching, Germany
[3] EMBL, D-69117 Heidelberg, Germany
[4] CRG, Barcelona 08003, Spain
关键词
NMR; Polycomblike; Pcl; PRC2; Tudor; aromatic cage; methyllysine; sDMA; post-translational modification; transcriptional regulation; SECONDARY-STRUCTURE; NMR; RECOGNITION; BINDING; GENE; METHYLATION; DYNAMICS; SMN; RNA; TRIMETHYLATION;
D O I
10.1002/pro.476
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1906 / 1916
页数:11
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