嗜肺军团菌SidEs介导非经典泛素化的调控机制  

Regulatory Mechanisms of Non-classical Ubiquitination Mediated by SidE Family Proteins of Legionella pneumophila

作　　者：甘梦柔 黄诗晴 关洪鑫 GAN Meng-Rou;HUANG Shi-Qing;GUAN Hong-Xin(Department of Biological Sciences,College of Life Science,Fujian Normal University,Fuzhou 350117,China)

机构地区：[1]福建师范大学生命科学学院生物科学系,福州350117

出　　处：《中国生物化学与分子生物学报》2025年第1期79-88,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.82225028,82172287,31900879,32171265);国家重点研发项目(No.2021YFC2301403)资助。

摘　　要：泛素化修饰(ubiquitination)是一种重要的蛋白质翻译后修饰,可以引起底物蛋白质稳定性、细胞定位和活性的改变,从而广泛参与细胞重要的生命活动。嗜肺军团菌(Legionella pneumophila)作为一种胞内寄生菌,通过特有的IVB型分泌系统(type IVB secretion system,T4BSS)向宿主释放300多种效应蛋白质,并利用这些效应蛋白质调节宿主细胞的生理活动,从而促进自身的生长和繁殖,并最终引起人类的军团病。在感染宿主的过程中,有多种效应蛋白质参与调控宿主细胞的泛素化系统。其中,SidEs协同SidJ、SdjA、DupA/DupB以及LnaB和MavL精密的、动态的调控宿主细胞的泛素化通路,为嗜肺军团菌的生存提供适宜的生存环境。近期,随着LnaB和MavL生物学功能的解析,嗜肺军团菌这一复杂的非经典泛素化调控循环得以基本阐明。鉴于此,本文总结了SidEs介导的非经典泛素化修饰的结构和酶学基础,以及其调控宿主细胞内质网重排和促进嗜肺军团菌液泡(Legionella-containing vacuole,LCV)形成的生物学意义;SidJ/SdjA调控SidEs磷酸核糖泛素化活性的机制;以及DupA/DupB、LnaB和MavL通过多步催化反应,逆转SidEs对宿主底物蛋白质泛素化修饰的催化机制。总之,本文将为深入理解该类型非经典泛素化修饰调控的详细机制及生物学意义提供参考,也为进一步理解嗜肺军团菌的致病机制提供帮助。Ubiquitination represents a critical post-translational modification of proteins,capable of inducing alterations in the stability,cellular localisation and activity of substrate proteins.Consequently,it plays a pivotal role in a multitude of essential cellular processes.The intracellular parasite Legionella pneumophila releases in excess of 300 effector proteins into its host cell via its distinctive type IVB secretion system.These effector proteins regulate the physiological activity of host cells,thereby facilitating the growth and reproduction of Legionella and ultimately resulting in Legionella infection in humans.In the context of host infection,a number of effector proteins have been identified as regulators of the host cell ubiquitination system.Together with SidJ,SdjA,DupA/DupB,LnaB,and MavL,SidEs precisely and dynamically modulate the ubiquitination pathway of host cells,thereby providing a suitable environment for L.pneumophila to survive.The clarification of the biological functions of LnaB and MavL has led to the elucidation of this complex non-canonical ubiquitination regulatory cycle in L.pneumophila.This review presents a summary of the structural and enzymatic basis of non-classical ubiquitination mediated by SidEs,along with an examination of its biological significance in regulating endoplasmic reticulum rearrangement and promoting Legionella-containing vacuole formation in host cells;the mechanism by which SidJ/SdjA regulates the phosphoribosylation activity of SidEs;and DupA/DupB,LnaB and MavL reverse the ubiquitination of host substrate proteins by SidEs through a multi-step catalytic reaction.In conclusion,this study will provide a reference for further understanding the detailed mechanism and biological significance of this type of non-classical ubiquitination modification,as well as offering insights into the pathogenic mechanism of L.pneumophila.

关 键 词：嗜肺军团菌 效应蛋白质 非经典泛素化 

分 类 号：Q71[生物学—分子生物学]