结核分枝杆菌ESX-1分泌蛋白EspB结构和功能分析

发布时间：2018-04-25 13:14

  本文选题：结核分枝杆菌 + EspB　； 参考：《生物化学与生物物理进展》2017年05期

【摘要】：结核分枝杆菌作为肺结核病的病原菌,在人类中致死率远高于其他病原菌.结核分枝杆菌具有特殊的疏水性细胞壁结构,这种致密的细胞壁结构帮助结核分枝杆菌抵御外界环境压力和来自宿主细胞的毒素.同时,它利用特殊的分泌系统将体内的毒力蛋白输出体外,ESX-1分泌系统就是其中之一.结核分枝杆菌ESX-1系统在结核分枝杆菌进入宿主细胞吞噬小体、逃逸至细胞质以及杀死吞噬细胞这些过程中发挥重要作用.研究表明,在结核分枝杆菌内膜上存在一个由多亚基组成、旨在帮助结核分枝杆菌向外输送分泌蛋白的分泌装置.在这个分泌装置的帮助下,结核分枝杆菌重要的毒力蛋白ESAT-6跨内膜向外分泌,EspB也通过这个内膜上的分泌装置被转运至胞外.EspB存在于静置培养的结核分枝杆菌的胶囊层中,也可在振荡培养的结核分枝杆菌的培养液中被检测.通过X射线晶体衍射分析,我们解析了EspB的晶体结构,相比于其他同源结构,发现了EspB的不同构象,即EspB单体能够自组装成为七聚体的规则结构,联系其与毒力因子ESAT-6具有共分泌的特点,七聚体构象的发现为解释EspB在结核分枝杆菌向外分泌蛋白的过程中发挥的作用提供线索,即EspB具有锚定在结核分枝杆菌胶囊层中,作为运输ESAT-6的孔道而存在的可能.
[Abstract]:As a pathogen of pulmonary tuberculosis, Mycobacterium tuberculosis has a higher mortality rate in humans than other pathogens. Mycobacterium tuberculosis has a special hydrophobic cell wall structure which helps Mycobacterium tuberculosis withstand environmental pressures and toxins from host cells. At the same time, it uses the special secretion system to export virulence protein in vivo to in vitro ESX-1 secretion system is one of them. Mycobacterium tuberculosis ESX-1 system plays an important role in the process of mycobacterium tuberculosis entering host cell phagocytosome escaping to cytoplasm and killing phagocyte. It has been shown that there is a secretory device composed of multiple subunits on the intima of Mycobacterium tuberculosis, which is designed to help mycobacterium tuberculosis transport secretory protein outward. With the help of this secretory device, ESAT-6, an important virulence protein of Mycobacterium tuberculosis, is also transported to the extracellular layer of Mycobacterium tuberculosis through the transintimal secretory device. EspB exists in the capsule layer of Mycobacterium tuberculosis in static culture. It can also be detected in the medium of oscillating culture of Mycobacterium tuberculosis. The crystal structure of EspB was analyzed by X-ray crystal diffraction. Compared with other homologous structures, we found different conformation of EspB, that is, the regular structure of EspB monomers can self-assemble into heptopolymer. In connection with the co-secretion of EspB with virulence factor ESAT-6, the octamer conformation provides clues for explaining the role of EspB in the process of mycobacterium tuberculosis into exocrine protein, that is, EspB is anchored in the capsule layer of Mycobacterium tuberculosis. The possibility of being a channel for transporting ESAT-6.
【作者单位】： 中国科学院生物物理研究所生物大分子国家重点实验室;中国科学院大学;
【基金】：中国科学院战略性先导科技专项(XDB08020202) 国家生物大分子重点实验室资助项目~~
【分类号】：R378.911
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本文编号：1801488