Structure and ligand of a histone acetyltransferase bromodomain
Structure and ligand of a histone acetyltransferase bromodomain
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作者：
Dhalluin, C;Carlson, JE;Zhou, MM
组蛋白乙酰化在染色质重塑和基因活化中很重要（1-4）。几乎所有已知的组蛋白乙酰转移酶（HAT）相关转录共激活因子都含有溴结构域，其类似于在许多染色质相关蛋白中发现的110个氨基酸的模块（5-9）。尽管这些布罗莫结构域广泛存在，但它们的三维结构和结合伴侣仍然未知。在这里，我们报告了HAT共激活因子P/CAF（p300/CBP相关因子）的布罗莫结构域的溶液结构（10，11）。结构揭示了一个不寻常的左手上下四螺旋束。此外，我们通过结构和定点诱变研究的组合表明，溴结构域可以与乙酰化赖氨酸特异性相互作用，使它们成为第一个这样做的已知蛋白质模块。P/CAF溴结构域识别乙酰赖氨酸的性质与组蛋白乙酰转移酶识别乙酰辅酶A的性质相似。因此，布罗莫结构域在基因转录调节中与共激活因子的HAT活性功能相关。
Histone acetylation is important in chromatin remodelling and gene activation(1-4). Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are similar to 110-amino-acid modules found in many chromatin-associated proteins(5-9). Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor)(10,11). The structure reveals an unusual left-handed up-and-down four-helix bundle. In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so, The nature of the recognition of acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. Thus, the bromodomain is functionally linked to the HAT activity of co-activators in the regulation of gene transcription.