蛋白翻译后修饰对蛋白的结构和功能起着非常重要的调节作用，赖氨酸琥珀酰化是中科院上海药物研究所和芝加哥大学共同合作在原核和真核细胞中最新发现的蛋白翻译后修饰通路。

  上海药物研究所的研究团队开创性地对哺乳动物细胞中的去乙酰化修饰酶Sirt5调控的琥珀酰化修饰底物进行了系统的蛋白质组学研究，发现了琥珀酰化修饰对能量代谢中的关键酶的调控作用，文章相继发表在Nature Chemical Biology和Molecular Cell上。但在原核生物中，控制该修饰的琥珀酰化底物及调节酶仍然未知，成为该修饰在原核生物研究的障碍。

　　上海药物所化学蛋白质组学中心和芝加哥大学通过进一步合作，系统研究了大肠杆菌中的琥珀酰化修饰底物，并发现了该修饰的调节酶CobB。此次研究在大肠杆菌中发现了670个蛋白上的2580个赖氨酸琥珀酰修饰位点，是原核生物中赖氨酸琥珀酰修饰研究的第一批数据资料。同时还在782个蛋白中找到了2803个乙酰化修饰位点，获得了野生型大肠杆菌中最大的赖氨酸乙酰化修饰数据库。

　　此项研究首次通过定性定量分析揭示了高糖营养环境的赖氨酸琥珀酰动态变化网络，表明高糖环境可以导致琥珀酰化和乙酰化修饰的显著增加，并对琥珀酰化修饰的影响更大，揭示了赖氨酸琥珀酰化在原核生物中为一高丰度修饰。 

   研究还首次发现了原核生物中的去琥珀酰修饰酶-CobB（类Sir2细菌赖氨酸去乙酰化酶），表明该酶具有赖氨酸去琥珀酰化和去乙酰化双重功能活性，提示其他乙酰化调节酶也可能有多种酶活性。此次研究为原核生物中赖氨酸琥珀酰化和乙酰化功能性研究提供了丰富的资源。

原文摘要：

Identification of Lysine Succinylation Substrates and the Succinylation Regulatory Enzyme CobB in Escherichia coli

Abstract
Lysine succinylation is a newly identified protein post-translational modification pathway present in both prokaryotic and eukaryotic cells. However, succinylation substrates and regulatory enzyme(s) remain largely unknown, hindering the biological study of this modification. Here we report the identification of 2,580 bacterial lysine succinylation sites in 670 proteins and 2,803 lysine acetylation (Kac) sites in 782 proteins, representing the first lysine succinylation dataset and the largest Kac dataset in wild-type E. coli. We quantified dynamic changes of the lysine succinylation and Kac substrates in response to high glucose. Our data showed that high-glucose conditions led to more lysine-succinylated proteins and enhanced the abundance of succinyllysine peptides more significantly than Kac peptides, suggesting that glucose has a more profound effect on succinylation than on acetylation. We further identified CobB, a known Sir2-like bacterial lysine deacetylase, as the first prokaryotic desuccinylation enzyme. The identification of bacterial CobB as a bifunctional enzyme with lysine desuccinylation and deacetylation activities suggests that the eukaryotic Kac-regulatory enzymes may have enzymatic activities on various lysine acylations with very different structures. In addition, it is highly likely that lysine succinylation could have unique and more profound regulatory roles in cellular metabolism relative to lysine acetylation under some physiological conditions.

打赏

下载安捷伦电子书《通过细胞代谢揭示新的药物靶点》探索如何通过代谢分析促进您的药物发现研究

10x Genomics新品Visium HD 开启单细胞分辨率的全转录组空间分析！

欢迎下载Twist《不断变化的CRISPR筛选格局》电子书

单细胞测序入门大讲堂 - 深入了解从第一个单细胞实验设计到数据质控与可视化解析

下载《细胞内蛋白质互作分析方法电子书》