Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A
Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A
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DOI：
10.1126/science.1125162
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发表时间：
2006-05-05
期刊：
影响因子：
56.9
通讯作者：
Xu, RM
中科院分区：
文献类型：
--
作者：
Huang, Y;Fang, J;Xu, RM
对组蛋白甲基化的生物学反应关键取决于“效应”蛋白对甲基 - 赖氨酸信号的准确解读和转导，然而到目前为止，我们对甲基 - 赖氨酸识别的理解仅限于对染色质结构域和WD40重复蛋白与组蛋白结合的研究。JMJD2A（一种含Jmjc结构域的组蛋白去甲基化酶）的双都铎结构域结合甲基化的组蛋白H3 - K4和H4 - K20。我们发现双都铎结构域具有交错结构，这种不寻常的折叠对其结合甲基化组蛋白尾部的能力是必需的。JMJD2A双都铎结构域与三甲基化H3 - K4肽的共晶结构显示，三甲基 - K4结合在由三个芳香族残基构成的笼状结构中，其中两个来自都铎 - 2基序，而结合特异性由涉及都铎 - 1基序氨基酸的侧链相互作用决定。我们的研究为都铎结构域对甲基化组蛋白尾部的识别提供了机制方面的见解，并揭示了两个紧密间隔的效应结构域对甲基 - 赖氨酸识别的结构复杂性。
Biological responses to histone methylation critically depend on the faithful readout and transduction of the methyl-lysine signal by "effector'' proteins, yet our understanding of methyl-lysine recognition has so far been limited to the study of histone binding by chromodomain and WD40-repeat proteins. The double tudor domain of JMJD2A, a Jmjc domain - containing histone demethylase, binds methylated histone H3-K4 and H4-K20. We found that the double tudor domain has an interdigitated structure, and the unusual fold is required for its ability to bind methylated histone tails. The cocrystal structure of the JMJD2A double tudor domain with a trimethylated H3-K4 peptide reveals that the trimethyl-K4 is bound in a cage of three aromatic residues, two of which are from the tudor-2 motif, whereas the binding specificity is determined by side-chain interactions involving amino acids from the tudor-1 motif. Our study provides mechanistic insights into recognition of methylated histone tails by tudor domains and reveals the structural intricacy of methyl-lysine recognition by two closely spaced effector domains.