The First Identification of Lysine Malonylation Substrates and Its Regulatory Enzyme
The First Identification of Lysine Malonylation Substrates and Its Regulatory Enzyme
复制标题
DOI：
10.1074/mcp.m111.012658
复制
发表时间：
2011-12-01
影响因子：
7
通讯作者：
Zhao, Yingming
中科院分区：
文献类型：
--
作者：
Peng, Chao;Lu, Zhike;Zhao, Yingming
蛋白质翻译后修饰（PTM）在赖氨酸残基，如赖氨酸甲基化，乙酰化和泛素化，是多样的，丰富的，和动态的。它们在调节多种细胞生理学中起关键作用。在这里，我们报告发现了一种新型的赖氨酸PTM，赖氨酸丙二酰化（Kmal）。Kmal最初通过质谱和蛋白质序列数据库搜索检测到。通过Western印迹、串联MS和合成肽的高效液相色谱、同位素标记和多种Kmal底物蛋白的鉴定，全面验证了该修饰。Kmal是在哺乳动物细胞和细菌细胞中观察到的动态和进化上保守的PTM。此外，我们证明，Sirt 5，III类赖氨酸脱乙酰酶的成员，可以催化赖氨酸脱丙二酰和赖氨酸脱琥珀酰反应在体外和体内。这一结果表明，其他III类赖氨酸脱乙酰酶，特别是那些没有明显的乙酰化蛋白质底物的非脱乙酰化活性的可能性。因此，我们的研究结果揭示了一种新型的PTM途径，并确定了第一个酶，可以调节赖氨酸丙二酰化和赖氨酸琥珀酰化状态。Molecular & Cellular Proteomics 10：10.1074/mcp. M111.012658，1-12，2011.
Protein post-translational modifications (PTMs) at the lysine residue, such as lysine methylation, acetylation, and ubiquitination, are diverse, abundant, and dynamic. They play a key role in the regulation of diverse cellular physiology. Here we report discovery of a new type of lysine PTM, lysine malonylation (Kmal). Kmal was initially detected by mass spectrometry and protein sequence-database searching. The modification was comprehensively validated by Western blot, tandem MS, and high-performance liquid chromatography of synthetic peptides, isotopic labeling, and identification of multiple Kmal substrate proteins. Kmal is a dynamic and evolutionarily conserved PTM observed in mammalian cells and bacterial cells. In addition, we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo. This result suggests the possibility of nondeacetylation activity of other class III lysine deacetylases, especially those without obvious acetylation protein substrates. Our results therefore reveal a new type of PTM pathway and identify the first enzyme that can regulate lysine malonylation and lysine succinylation status. Molecular & Cellular Proteomics 10: 10.1074/mcp.M111.012658, 1-12, 2011.