细菌中Ⅰ型毒素蛋白与细胞膜相互作用机制的研究进展  

Research Progress on Interaction Mechanisms of TypeⅠToxin Protein-membrane in Bacteria

作　　者：于茹 赵立岭[1] 李娥娥 陈明翠 赵立 郭陈刚 于家峰 曹赞霞 YU Ru;ZHAO Li-Ling;LI E-E;CHEN Ming-Cui;ZHAO Li;GUO Chen-Gang;YU Jia-Feng;CAO Zan-Xia(Shandong Provincial Key Laboratory of Biophysics,Institute of Biophysics,Dezhou University,Dezhou 253023,China)

机构地区：[1]山东省生物物理重点实验室,德州学院生物物理实验室,德州253023

出　　处：《生物化学与生物物理进展》2022年第10期1974-1986,共13页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(32171249,61771093,31670727);山东省自然科学基金(ZR2016CQ15,ZR2020QC124);山东省教育厅青创人才引育计划资助项目。

摘　　要：Ⅰ型毒素-抗毒素(TA)系统在细菌基因组中广泛存在,在细菌的生长、生存中发挥多种生物学功能,包括抗菌、红细胞毒性、促进持留菌形成、抑制细菌生长或导致细菌休眠等。绝大部分Ⅰ型毒素蛋白以细胞膜作为靶标,目前已知的一种作用机制是在细胞膜上形成孔洞结构,造成膜电位的下降或细胞膜的破坏,从而抑制ATP的合成或导致细菌死亡;另一种可能的作用机制是毒素蛋白作用在细胞膜上,改变细胞的形状,导致细胞进入休眠状态。Ⅰ型毒素蛋白-细胞膜作用机制的复杂性和生物功能的多样性远超预期。因此,解析Ⅰ型毒素蛋白在不同细胞膜中的组装机制及其所形成结构特征就变得非常重要,这也是揭示其结构-功能关系的关键。本文通过综述已报道的Ⅰ型TA系统的结构特征与生物学功能,结合对其跨膜结构域的预测,探讨了其可能在细胞膜中形成的不同结构及其对功能的影响,分析了影响作用机制的关键因素。这些研究既给耐药细菌的治疗带来机遇,又为新型抗菌药物的研发带来思路。The typeⅠtoxin-antitoxin(TA)system is widespread in the bacterial genome and can play a variety of biological functions in the growth and survival of bacteria,including antibacterial function,red blood cell toxicity,promoting the formation of persistent bacteria,inhibiting bacterial growth,or causing bacterial dormancy,etc.The vast majority of typeⅠtoxin proteins target the cell membrane.One known mechanism of action is the formation of pores in the cell membrane,resulting in a decrease in membrane potential or destruction of the cell membrane,thereby inhibits the ATP synthesis or leads to the bacterial death;another possible mechanism of action is that the toxin proteins act on the cell membrane,changing the shape of the cell and causing it to enter a dormant state.The complexity of the typeⅠtoxin protein-membrane mechanism and the diversity of its biological functions are much more complex beyond our expectations.Therefore,it is important to analyze the assembly mechanism of typeⅠtoxin protein in different membranes and their structural characteristics,which is also the key to revealing its structure-function relationship.This article summarizes the reported structural characteristics and biological functions of the typeⅠTA system,explores the formation of different structures in the cell membrane that affect its function combined with the prediction of its transmembrane domains,and analyzes the key factors affecting its mechanism of action.It brings opportunities for the treatment of drug-resistant bacteria,and also brings ideas for the research of new antibacterial drugs.

关 键 词：毒素-抗毒素系统 Ⅰ型毒素蛋白 结构特征 生物学功能 耐药菌 

分 类 号：Q7[生物学—分子生物学] Q93