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在Legionella物种中保存的乙转移酶效应体准了真核生物eIF3复合体,以调节蛋白质翻译

Lukas Syriste¹, Deepak T Patel¹, Peter J Stogios²

¹Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.

|February 9, 2024

概括

军团菌细菌使用VipF效应器通过乙化真核细胞转化启动因子3复合体来抑制宿主细胞蛋白转化. 这项研究揭示了这些保存的细菌毒性因子的分子功能.

科学领域:

微生物学微生物学
结构生物学结构生物学
分子生物学分子生物学

背景情况:

军团菌种类. 军团菌种. 是细胞内病原体,它们利用Dot/Icm类型IVb分泌系统将蛋白质效应物送入宿主细胞.
虽然效应因子的谱系各不相同,但"核心"效应因子的保留子集表明,在Legionella物种中存在共同的致病策略,尽管它们的功能在很大程度上是未知的.
来自Legionella pneumophila的Lpg0103 (VipF) 疗效器是一个核心疗效器,含有Gcn5相关的N-乙转移酶 (GNAT) 协奏组域.

研究的目的:

为了阐明维普F的结构和功能,维普F是一种保存的军团菌效应蛋白.
研究VipF.的酶活性和宿主相互作用.
了解VipF在军团菌病原发生中的作用.

主要方法:

用X射线晶体学来确定与乙-CoA.复合体中的Legionella hackeliae Lha0223 (一种VipF同类物) 的结构.
在体外的酶定量测试以评估VipF对各种基质的乙转移酶活性.
同免疫沉用于识别与Lpg0103.3的宿主蛋白相互作用.
在体外蛋白转化试验评估VipF活动对宿主转化的影响.

主要成果:

Lha0223的晶体结构显示了两个GNAT域的保存折叠,只有C端域表现出催化活性.
在VipF中,乙转移酶对小分子,聚-L-lysine和基因素衍生的活性得到了证明.
发现VipF (Lpg0103) 与人类真核细胞转化启动因子3 (eIF3) 的K子单元相互作用.
在eIF3-K的C端尾上,VipF乙化了氨酸残留物,从而在体外抑制了eIF3-介导的蛋白转化.

结论:

该VipF效应器家族作为一对联GNAT酶起作用,其C终端域具有催化活性.
VipF的目标是人类的eIF3复合体,特别是乙化eIF3-K.
通过VipF介导的乙化抑制了真核蛋白转化,这代表了莱吉欧内拉病原菌的新型机制.

关键词:

流感性肺炎菌 (Legionella pneumophila) 是一种流感性肺炎菌.乙烯基转移酶的使用方法效应器效应器是一个效应器.病变的发生和发病.

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