Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9
Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9
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DOI：
10.1038/nature722
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发表时间：
2002-03-07
期刊：
影响因子：
64.8
通讯作者：
Laue, ED
中科院分区：
文献类型：
--
作者：
Nielsen, PR;Nietlispach, D;Laue, ED
组蛋白的特定修饰是基本的表观遗传标记(1)--基因表达的可遗传变化，不影响DNA序列。组蛋白H3中赖氨酸9的甲基化是由异染色质蛋白1(HP1)识别的，它指导其他蛋白质的结合来控制染色质结构和基因表达(2-4)。在这里，我们表明HP1使用诱导适配机制来识别这种修饰，正如它的色域与组蛋白H3肽结合在赖氨酸9的Nzeta上的二甲基化所揭示的那样。N-甲基的结合口袋由三个芳香族侧链提供，Tyr 21，Trp 42和Phe 45，它们位于两个区域，在多肽结合时变得有序。Lys 9的侧链几乎完全伸展，并被许多其他染色质域中保守的残基包围。Lys 9之前的QTAR肽序列与染色域发生了大部分额外的相互作用，HP1残基Val23、Leu 40、Trp 42、Leu 58和Cys 60似乎是特异性的主要决定因素，因为它们结合了关键的掩埋的Ala 7。这些发现预测了其他哪些染色域将与甲基化蛋白结合，并提出了它们识别的基序。
Specific modifications to histones are essential epigenetic markers(1)-heritable changes in gene expression that do not affect the DNA sequence. Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression(2-4). Here we show that HP1 uses an induced-fit mechanism for recognition of this modification, as revealed by the structure of its chromodomain bound to a histone H3 peptide dimethylated at Nzeta of lysine 9. The binding pocket for the N-methyl groups is provided by three aromatic side chains, Tyr 21, Trp 42 and Phe 45, which reside in two regions that become ordered on binding of the peptide. The side chain of Lys 9 is almost fully extended and surrounded by residues that are conserved in many other chromodomains. The QTAR peptide sequence preceding Lys 9 makes most of the additional interactions with the chromodomain, with HP1 residues Val 23, Leu 40, Trp 42, Leu 58 and Cys 60 appearing to be a major determinant of specificity by binding the key buried Ala 7. These findings predict which other chromodomains will bind methylated proteins and suggest a motif that they recognize.