美国普渡大学罗招庆研究组和福建师范大学欧阳松应研究组合作发现了钙调蛋白依赖型谷氨酸化酶对磷酸核糖泛素化的调控。2019年8月15日，国际知名学术期刊《自然》发表了这一成果。

研究人员证明SidJ通过诱导谷氨酸基团共价连接到SidE家族SdeA成员的E860氨基酸位点来抑制SidE的活性，E860是泛素激活中涉及的单-ADP-核糖基转移酶活性所需的催化残基之一。SidJ的这种抑制在宿主细胞中是空间限制的，因为其活性需要真核生物特异性蛋白钙调蛋白（CaM）。研究人员解析了包含AMP的SidJ-CaM复合物结构，发现该反应中使用的ATP在磷酸位置被SidJ切割，这在没有谷氨酸或可修饰的SdeA的情况下进行自身AMP化。这些研究结果揭示了细菌致病性的调控机制，即抑制毒力因子活性的谷氨酸化反应被宿主因子依赖性酰基腺苷化激活。

据介绍，细菌病原体嗜肺军团菌通过Dot/Icm分泌系统递送的数百种效应蛋白广泛调节宿主细胞功能，从而创造细胞内微环境允许其复制。其中，SidE家族的成员通过独特的磷酸核糖泛素化机制调控几种细胞过程，该机制绕过了经典的泛素化机制。SidE的活性受另一个称为SidJ的Dot/Icm效应蛋白的调控；然而，这一调控的机制尚不完全清楚。

FC碰碰胡老虎机法典-提高赢钱机率的下注技巧阅读：

罗招庆

罗招庆，美国普渡大学生物科学系教授。研究方向为嗜肺军团菌（Legionella pneumophila) 致病机理和寄主免疫反应。（据西南民族大学）

欧阳松应

欧阳松应，福建师范大学教授，博士生导师，生命科学学院院长。主要研究方向：运用X射线晶体学、冷冻电镜和其它生物物理技术研究病原体感染和宿主天然免疫反应的分子机制。（据福建师范大学）

附：英文原文

Title: Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase

Author: Ninghai Gan, Xiangkai Zhen, Yao Liu, Xiaolong Xu, Chunlin He, Jiazhang Qiu, Yancheng Liu, Grant M. Fujimoto, Ernesto S. Nakayasu, Biao Zhou, Lan Zhao, Kedar Puvar, Chittaranjan Das, Songying Ouyang, Zhao-Qing Luo

Issue&Volume: Volume 572 Issue 7769

Abstract: The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating host-cell functions using hundreds of effector proteins delivered by its Dot/Icm secretion system1. Among these, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism that bypasses the canonical ubiquitination machinery24. The activity of SidEs is regulated by another Dot/Icm effector known as SidJ5; however, the mechanism of this regulation is not completely understood6,7. Here we demonstrate that SidJ inhibits the activity of SidEs by inducing the covalent attachment of glutamate moieties to SdeAa member of the SidE familyat E860, one of the catalytic residues that is required for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation2. This inhibition by SidJ is spatially restricted in host cells because its activity requires the eukaryote-specific protein calmodulin (CaM). We solved a structure of SidJCaM in complex with AMP and found that the ATP used in this reaction is cleaved at the -phosphate position by SidJ, whichin the absence of glutamate or modifiable SdeAundergoes self-AMPylation. Our results reveal a mechanism of regulation in bacterial pathogenicity in which a glutamylation reaction that inhibits the activity of virulence factors is activated by host-factor-dependent acyl-adenylation.

DOI: 10.1038/s41586-019-1439-1

Source:https://www.nature.com/articles/s41586-019-1439-1