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中国防痨杂志 ›› 2014, Vol. 36 ›› Issue (6): 509-513.doi: 10.3969/j.issn.1000-6621.2014.06.020

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分枝杆菌中原核类泛素蛋白化靶蛋白的功能分析

薛玉 刘毅 张旭霞 张俊杰 李传友     注:薛玉与刘毅为共同第一作者   

  1. 101149  北京市结核病胸部肿瘤研究所  首都医科大学附属北京胸科医院  北京市耐药结核病重点实验室细菌免疫室(薛玉、刘毅、张旭霞、李传友);北京师范大学细胞增殖调控教育部重点实验室(刘毅、张俊杰)
  • 收稿日期:2014-05-02 出版日期:2014-06-10 发布日期:2014-06-28
  • 通信作者: 李传友 E-mail:lichuanyou6688@hotmail.com
  • 基金资助:

    国家自然科学基金(31170064);北京市优秀人才项目(2011D003034000013)

A functional analysis of the proteins targeted by prokaryotic ubiquitin-like protein (Pup) in mycobacteria

XUE Yu, LIU Yi, ZHANG Xu-xia, ZHANG Jun-jie, LI Chuan-you   

  1. Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital of Capital Medical University, Beijing 101149, China
  • Received:2014-05-02 Online:2014-06-10 Published:2014-06-28
  • Contact: LI Chuan-you E-mail:lichuanyou6688@hotmail.com

摘要: 分枝杆菌中存在一种类似真核生物泛素的小分子蛋白,称为原核类泛素蛋白(prokaryotic ubiquitin-like protein, Pup),蛋白被Pup共价标记后,或被蛋白酶体降解或参与修饰后的调节作用,可影响细菌活动的各个环节。结核分枝杆菌中目前发现可被Pup标记的共有58种蛋白;耻垢分枝杆菌被标记了41种蛋白,其中38种都可以在结核分枝杆菌中找到同源蛋白。这些标记后的靶蛋白涉及了至少6种机制和功能,包括分枝杆菌的毒力、信号通路、脂类的合成、细胞壁和(或)膜的合成、中间代谢,等等。其中大部分蛋白被标记后经由蛋白酶体降解,也有被Pup标记的蛋白参与信号传导和调控作用;通过对这些靶蛋白的比较分析,能够对结核分枝杆菌的耐药和致病机制提供进一步的解释,同时这些Pup标记的蛋白也可以作为潜在的药物靶点,对其的分析研究可为结核病的治疗和控制提供理论基础。

关键词: 分枝杆菌属, 泛素类, 蛋白酶体内肽酶复合物

Abstract: Prokaryotic ubiquitin-like protein (Pup), a small protein alike to the ubiquitin in eukaryotes, exi-sts in mycobacterium. When targeted by the Pup, the proteins are degraded by the proteasome or become regulators after the modification. Thus, it can influence all activities of the cells. Currently, 58 population proteins, which can be targeted by Pup, have been identified in Mycobacterium tuberculosis (Mtb); in Mycobacterium smegmatis, it has been identified that 41 population proteins can be targeted by Pup, and the orthologous genes of 38 out of 41 population proteins can be found in Mtb genome. Those target proteins have been involved in at least 6 mechanisms and functions in the activities of the cells, including the virulence of mycobacterium, information pathway, lipid metabolism, cell wall and/or membrane synthesis, and intermediary metabolism, etc. After targeted, most of the population proteins are degrated by the proteasome and only a few of them are involved in the signal transmissions and re-gulations. Through comparisons and analysis of the target proteins, the further explanations can be made for the mechanisms of Mtb drug-resistance development and pathopoiesis; at the same time, the proteins targeted by Pup can be the potential drug targets, which provides the theory foundations for the TB treatment and control.

Key words: Mycobacterium, Ubiquitins, Proteasome endopeptidase complex