Structure of an atypical Tudor domain in the Drosophila Polycomblike protein
Structure of an atypical Tudor domain in the Drosophila Polycomblike protein
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DOI：
10.1002/pro.476
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发表时间：
2010-10-01
期刊：
影响因子：
8
通讯作者：
Sattler, Michael
中科院分区：
文献类型：
--
作者：
Friberg, Anders;Oddone, Anna;Sattler, Michael
组蛋白尾部的翻译后修饰是最突出的表观遗传标记之一，在染色质水平的转录控制中起着关键作用。Polycomblike （Pcl）蛋白是组蛋白甲基转移酶复合物（Pcl- prc2）的一部分，负责高水平的组蛋白H3 K27三甲基化。对果蝇幼虫的研究表明，Pcl是将Pcl- prc2锚定在靶基因上所必需的，但这是如何实现的尚不清楚。Pcl包括一个都铎域和两个PHD指。已知这些结构域识别甲基化赖氨酸或精氨酸残基，并可能有助于靶向Pcl-PRC2。在这里，我们报道了果蝇Pcl (Pcl-Tudor) Tudor结构域的核磁共振结构和与假定配体的结合研究。Pcl-Tudor含有一个非典型的，不完全芳香笼，不与已知的Tudor结构域配体，如甲基化赖氨酸或精氨酸相互作用。有趣的是，人类Pcl同源物表现出完整的芳香笼，表明它们可能识别甲基化赖氨酸。与其他Tudor结构域的结构比较表明，Pcl-Tudor可能通过暴露的疏水表面斑块参与分子内或分子间的相互作用。
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.