Structural insight into the recognition of acetylated histone H3K56ac mediated by the bromodomain of CREB-binding protein.
Structural insight into the recognition of acetylated histone H3K56ac mediated by the bromodomain of CREB-binding protein.
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CREB 结合蛋白溴结构域介导的乙酰化组蛋白 H3K56ac 识别的结构洞察。
DOI：
10.1111/febs.14198
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发表时间：
2017
期刊：
影响因子：
5.4
通讯作者：
Ruan Ke
中科院分区：
文献类型：
--
作者：
Xu Li;Cheng Aimin;Huang Min;Zhang Jiahai;Jiang Yiyang;Wang Chongyuan;Li Fudong;Bao Hongyu;Gao Jia;Wang Na;Liu Jiuyang;Wu Jihui;Wong Catherine C L;Ruan Ke
组蛋白H3(H3K56ac)的赖氨酸56乙酰化增强了组蛋白伴侣与H3-H4二聚体的结合亲和力。CREB结合蛋白(CBP)具有识别H3K56乙酰化的溴结构域。CBP还具有组蛋白乙酰转移酶(HAT)结构域，该结构域可以促进游离组蛋白的H3K56乙酰化，从而便于将复制依赖的伴侣蛋白运送到乙酰化组蛋白以进行染色质组装。然而，CBP溴域识别H3K56ac的机制和发生这种识别的背景仍然难以捉摸。在这里，我们解决了CBP溴域与H3K56ac多肽的络合物的晶体结构。我们的数据表明，CBP溴域对H3K56ac具有高亲和力。结构和亲和力分析表明，CBP溴域偏好−2位的芳香族残基和−4位的精氨酸，并选择性地识别含有H3K56ac的H3αN螺旋的延伸构象。我们还证明了CBP溴域以重组的H3-H4二聚体与H3K56ac结合，而不是以单核小体的形式结合。我们的结果表明，CBP溴域选择性地识别H3-H4二聚体中K56-乙酰化的H3αN区域的扩展构象，这有望促进CBP的HAT活性，从而促进随后的H3K56游离组蛋白乙酰化。数据库本文所描述的CBP溴域与H3K56ac络合物的配位已经保存在PDB中，注册号为5GH9。
The acetylation of lysine 56 of histone H3 (H3K56ac) enhances the binding affinity of histone chaperones to H3–H4 dimers. CREB‐binding protein (CBP) possesses a bromodomain that recognizes H3K56 acetylation. CBP also possesses a histone acetyltransferase (HAT) domain, which has been shown to promote H3K56 acetylation of free histones to facilitate delivery of replication‐dependent chaperones to acetylated histones for chromatin assembly. However, the mechanism by which the CBP bromodomain recognizes H3K56ac and the context in which such recognition occurs remain elusive. Here, we solved the crystal structure of the CBP bromodomain in complex with an H3K56ac peptide. Our data demonstrate that the CBP bromodomain recognizes H3K56ac with high affinity. Structural and affinity analyses reveal that the CBP bromodomain prefers an aromatic residue at the −2 position and an arginine at the −4 position from the acetyl‐lysine, and that the CBP bromodomain selectively recognizes an extended conformation of the H3 αN helix that contains H3K56ac. We also demonstrate that the CBP bromodomain binds to H3K56ac in a recombinant H3–H4 dimer but not in a mono‐nucleosome. Our results suggest that the CBP bromodomain selectively recognizes an extended conformation of the K56‐acetylated H3 αNregion within an H3–H4 dimer, which is expected to facilitate the HAT activity of CBP for subsequent H3K56 acetylation of free histones.DatabasesCoordinates of the CBP bromodomain in complex with H3K56ac as described in this article have been deposited in the PDB with accession number 5GH9.