Structural Insights into Histone H3 Lysine 56 Acetylation by Rtt109
Structural Insights into Histone H3 Lysine 56 Acetylation by Rtt109
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DOI：
10.1016/j.str.2008.07.006
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发表时间：
2008-10-08
期刊：
影响因子：
5.7
通讯作者：
Yuan, Y. Adam
中科院分区：
文献类型：
--
作者：
Lin, Chengqi;Yuan, Y. Adam
组蛋白乙酰化对于许多基本细胞过程的调节起着重要作用。酿酒酵母Rtt 109是一类重要的组蛋白乙酰转移酶（HATs），它通过一种未知的机制直接乙酰化新合成的组蛋白H3赖氨酸56（H3-K56），从而促进基因组的稳定性。在这里，我们报告的晶体结构的Rtt 109在2.2埃和Rtt 109/乙酰辅酶A二元复合物在1.9埃。其结构为钳状拓扑结构，由混合的三层α/β模块构成中心模块，其核心区域类似于GCN 5 HAT结构域和P300/CBP HAT结构域的结构。利用结构和生化分析，我们发现了催化活性位点，并确定Asp 288为去质子化残基和Lys 290为自动乙酰化残基。我们进一步提出了独特的H3-K56锚定口袋和潜在的H3 α N结合沟。我们的工作为理解Rtt 109对H3-K56的乙酰化机制提供了结构上的见解。
Histone acetylation plays important roles for the regulation of many fundamental cellular processes. Saccharomyces cerevisiae Rtt109 is an important class of histone acetyltransferases (HATs), which promote genome stability by directly acetylating newly synthesized histone H3 lysine 56 (H3-K56) through an unknown mechanism. Here, we report the crystal structures of Rtt109 at 2.2 angstrom and Rtt109/Acetyl-CoA binary complex at 1.9 angstrom. The structure displays a vise-like topology with mixed three-layered alpha/beta module forming the central module, whose core region resembles the structure of GCN5 HAT domain and P300/CBP HAT domain. Using structural and biochemical analyses, we have discovered the catalytic active site and have identified Asp288 as the deprotonation residue and Lys290 as the autoacetylation residue. We have further proposed the unique H3-K56 anchoring pocket and the potential H3 alpha N binding groove. Our work has provided structural insights to understand the acetylation mechanism of H3-K56 by Rtt109.