Supramolecular assembly of KAT2A with succinyl-CoA for histone succinylation.
Supramolecular assembly of KAT2A with succinyl-CoA for histone succinylation.
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DOI：
10.1038/s41421-018-0048-8
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发表时间：
2018
期刊：
影响因子：
33.5
通讯作者：
Lu Z
中科院分区：
文献类型：
--
作者：
Wang Y;Guo YR;Xing D;Tao YJ;Lu Z
组蛋白修饰调节许多基本的生物学过程，包括DNA复制，转录和修复。组蛋白的18种翻译后修饰，包括乙酰化、琥珀酰化和甲基化，已被报道1-3。赖氨酸乙酰转移酶2A（KAT 2A，也称为GCN 5），GCN 5相关的N-乙酰转移酶超家族的成员，并且是Spt-Ada-KAT 2A-乙酰转移酶（佐贺）和Ada-two-A-containing复合物的组分，在1996年被鉴定为第一个转录相关的组蛋白乙酰转移酶4，5。KAT 2A结合乙酰辅酶A（CoA）并将其乙酰基转移到组蛋白上以调节染色质结构和位点特异性转录6.我们最近的研究报道KAT 2A还可以作为组蛋白琥珀酰转移酶通过将琥珀酰辅酶A上的琥珀酰基直接转移到组蛋白H3赖氨酸79（H3 K79）上，这对于调节肿瘤细胞中的基因表达是重要的7.为了阐明催化机制，我们使用X射线晶体学7确定了载脂蛋白和琥珀酰辅酶A复合的KAT 2A的结构。通过将这些结构与KAT 2A与乙酰辅酶A 7复合的结构进行比较，我们先前证明了琥珀酰辅酶A和乙酰辅酶A在KAT 2A的催化结构域中占据相似的结合位点，并鉴定了与酰基链7相互作用的关键残基。在目前的工作中，我们报告了一种新的高阶组装的催化结构域的KAT 2A中观察到的载脂蛋白和琥珀酰辅酶A复合物的晶体结构。值得注意的是，
Dear Editor, Histone modifications regulate many fundamental biological processes, including DNA replication, transcription, and repair. Eighteen posttranslational modifications of histones, including acetylation, succinylation, and methylation, have been reported 1–3. Lysine acetyltransferase 2A (KAT2A, also known as GCN5), a member of the GCN5-related N-acetyltransferase superfamily and a component of Spt-Ada-KAT2A-acetyltransferase (SAGA) and Ada-two-A-containing complexes, was identified as the first transcription-related histone acetyltransferase in 1996 4, 5. KAT2A binds to acetylcoenzyme A (CoA) and transfers its acetyl group to histones to regulate chromatin architecture and locusspecific transcription 6.Our recent studies reported that KAT2A can also function as a histone succinyltransferase by directly transferring the succinyl group from succinyl-CoA to histone H3 lysine 79 (H3K79), which is important for the regulation of gene expression in tumor cells 7. To elucidate the catalytic mechanism, we determined the structures of both the apo and succinyl-CoA-complexed KAT2A using X-ray crystallography 7. By comparing these structures with that of KAT2A in complex with acetyl-CoA 7, we previously demonstrated that succinyl-CoA and acetyl-CoA occupy similar binding sites in the catalytic domain of KAT2A and identified key residues interacting with the acyl chains 7. In the present work, we report a novel highorder assembly for the catalytic domain of KAT2A observed in the crystal structures of both the apo and succinyl-CoA complexes. It is important to note that both
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