SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones.
SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones.
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SIRT2 逆转组蛋白上的 4-氧壬酰赖氨酸修饰
DOI：
10.1021/jacs.6b04977
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发表时间：
2016-09-28
影响因子：
15
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Jin J;He B;Zhang X;Lin H;Wang Y
翻译后修饰（PTMs）调节许多蛋白质，对许多生物学过程很重要。赖氨酸4-氧代壬酰化（4-ONylation）是一种新发现的阻止核小体在氧化应激下组装的组蛋白PTM。是否存在从组蛋白中去除4-ONyl的细胞酶仍然未知，这阻碍了对该PTM的细胞功能的进一步研究。在这里，我们报告了哺乳动物SIRT 2可以从活细胞中的组蛋白和其他蛋白质中去除4-ONyl。SIRT 2与4-ONyl肽复合的晶体结构揭示了Phe 119与4-ONyl基团的酮氧之间的孤对-π相互作用。这是第一次报道逆转4-ONyl赖氨酸修饰的机制，将有助于理解SIRT 2在氧化应激反应中的作用和4-ONylation的功能。
Post-translational modifications (PTMs) regulate numerous proteins and are important for many biological processes. Lysine 4-oxononanoylation (4-ONylation) is a newly discovered histone PTM that prevents nucleosome assembly under oxidative stress. Whether there are cellular enzymes that remove 4-ONyl from histones remains unknown, which hampers the further investigation of the cellular function of this PTM. Here, we report that mammalian SIRT2 can remove 4-ONyl from histones and other proteins in live cells. A crystal structure of SIRT2 in complex with a 4-ONyl peptide reveals a lone pair-π interaction between Phe119 and the ketone oxygen of the 4-ONyl group. This is the first time that a mechanism to reverse 4-ONyl lysine modification is reported and will help to understand the role of SIRT2 in oxidative stress responses and the function of 4-ONylation.