BRD2 第二个溴结构域识别 K5/K12-二乙酰化组蛋白 H4 的结构意义。
Structural implications for K5/K12-di-acetylated histone H4 recognition by the second bromodomain of BRD2.
机构信息
RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama, Japan.
出版信息
FEBS Lett. 2010 Sep 24;584(18):3901-8. doi: 10.1016/j.febslet.2010.08.013. Epub 2010 Aug 13.
Abstract
The BET family proteins recognize acetylated chromatin through their two bromodomains, acting as transcriptional activators or tethering viral genomes to the mitotic chromosomes of their host. The structural mechanism for how the N-terminal bromodomain of human BRD2 (BRD2-BD1) deciphers the mono-acetylated status of histone H4 tail was recently reported. Here we show the crystal structure of the second bromodomain of BRD2 (BRD2-BD2) in complex with the di-acetylated histone H4 tail (H4K5ac/K12ac). To our surprise, a single K5ac/K12ac peptide interacts with two BRD2-BD2 molecules simultaneously: the K5ac residue binds to one BRD2-BD2 molecule while the K12ac residue binds to another. These results provide a structural basis for the recognition of two different patterns of the histone acetylation status by a single bromodomain.
摘要
BET 家族蛋白通过其两个溴结构域识别乙酰化染色质，充当转录激活因子或将病毒基因组固定在宿主的有丝分裂染色体上。最近报道了人 BRD2（BRD2-BD1）的 N 端溴结构域解析组蛋白 H4 尾部单乙酰化状态的结构机制。在这里，我们展示了 BRD2（BRD2-BD2）的第二个溴结构域与二乙酰化组蛋白 H4 尾部（H4K5ac/K12ac）复合物的晶体结构。令我们惊讶的是，单个 K5ac/K12ac 肽同时与两个 BRD2-BD2 分子相互作用：K5ac 残基与一个 BRD2-BD2 分子结合，而 K12ac 残基与另一个 BRD2-BD2 分子结合。这些结果为单个溴结构域识别两种不同的组蛋白乙酰化状态模式提供了结构基础。
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