A chemical reporter facilitates the detection and identification of lysine HMGylation on histones.
A chemical reporter facilitates the detection and identification of lysine HMGylation on histones.
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化学报告基因有助于检测和鉴定组蛋白上赖氨酸 HMG 化。
DOI：
10.1039/c8sc02483a
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发表时间：
2018-10-28
期刊：
影响因子：
8.4
通讯作者：
Li XD
中科院分区：
文献类型：
--
作者：
Bao X;Xiong Y;Li X;Li XD
化学报告基因HMGAM-yne有助于检测和鉴定组蛋白上赖氨酸的hmg酰化。赖氨酸3-羟基-3-甲基戊二酰化（HMG-K）是一种新发现的非酶性线粒体PTM。然而，这种新的PTM的底物范围尚未得到充分的探索，这极大地阻碍了对其调控机制和细胞功能的解释。在这里，我们报道了一个炔功能化化学报告（HMGAM-yne）的发展，用于检测和鉴定细胞hmgam基化蛋白。HMGAM-yne是细胞渗透性的，并通过代谢并入活细胞中的蛋白质中。随后的双正交共轭使HMG-K蛋白底物的荧光可视化和鉴定成为可能。使用HMGAM-yne，我们还发现Sirt5是调节细胞中hmg酰化的“橡皮擦”。除了已知的线粒体HMG-K蛋白，HMGAM-yne促进了多种核蛋白的发现，包括组蛋白，作为赖氨酸hmg酰化的新底物。
Chemical reporter, HMGAM-yne, facilitates the detection and identification of lysine HMGylation on histones. Lysine 3-hydroxyl-3-methylglutarylation (HMG-K) is a newly identified PTM that can occur non-enzymatically in mitochondria. However, the substrate scope of this new PTM remains insufficiently explored, which has greatly hindered the progress in interpreting its regulatory mechanisms and cellular functions. Here, we report the development of an alkyne-functionalized chemical reporter (HMGAM-yne), for the detection and identification of cellular HMGylated proteins. HMGAM-yne is cell-permeable and metabolically incorporated into proteins in living cells. Subsequent biorthogonal conjugation enables fluorescence visualization and identification of the protein substrates of HMG-K. Using HMGAM-yne, we also identified Sirt5 as an ‘eraser’ that regulates HMGylation in cells. In addition to the known mitochondrial HMG-K proteins, HMGAM-yne facilitates the discovery of multiple nuclear proteins, including histones, as novel substrates of lysine HMGylation.
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影响因子：
18.3
作者：
Hang, Howard C.;Wilson, John P.;Charron, Guillaume
通讯作者：
Charron, Guillaume
影响因子：
16
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Nishida Y;Rardin MJ;Carrico C;He W;Sahu AK;Gut P;Najjar R;Fitch M;Hellerstein M;Gibson BW;Verdin E
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Verdin E
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Wagner GR;Bhatt DP;O'Connell TM;Thompson JW;Dubois LG;Backos DS;Yang H;Mitchell GA;Ilkayeva OR;Stevens RD;Grimsrud PA;Hirschey MD
通讯作者：
Hirschey MD
影响因子：
3.9
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16.6
作者：
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通讯作者：
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