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Acta Cryst D:霍乱弧菌自身免疫保护机制研究取得新进展

  1. 霍乱弧菌
  2. 免疫保护
  3. 结构生物学

来源:生物谷 2014-04-04 12:01

近日,中科院生物物理所范祖森研究组和江涛研究组在Acta Cryst D在线发表了题为《Molecular mechanism for self-protection against the type VI secretion system in Vibrio cholerae》的有关细菌免疫保护机制研究的最新成果。

近日,中科院生物物理所范祖森研究组和江涛研究组在Acta Cryst D在线发表了题为《Molecular mechanism for self-protection against the type VI secretion system in Vibrio cholerae》的有关细菌免疫保护机制研究的最新成果。

霍乱弧菌具有典型的VI分泌系统,三种VgrG蛋白(VgrG1-3)围成三聚体形成VI分泌系统底部及针尖状结构。霍乱弧菌的VgrG3毒性酶能够水解细菌细胞壁的肽聚糖,发挥其裂解细菌活性。VgrG3蛋白C端含有肽聚糖结合区域(VgrG3PGB)和催化区域(VgrG3CD),它的酶活性能被其对应的免疫蛋白TsiV3所抑制。TsiV3基因缺失导致霍乱弧菌被同类杀死,丧失自我保护的能力,并且严重损害霍乱弧菌的致病能力。为了阐释VI型分泌系统的结构基础,研究团队获得了VgrG3CD与TsiV3蛋白复合物的晶体,解析了TsiV3与VgrG3酶活结构域(VgrG3CD)复合物的高分辨率(2.3埃)的晶体结构。结构分析显示,TsiV3与VgrG3CD通过4个相互作用界面形成了紧密的相互作用,通过一系列的点突变,发现Gln91和Arg92形成的第一个作用界面对VgrG3CD-TsiV3复合物的形成最为重要。研究团队进一步发现,TsiV3以稳定的双体形式存在,单体的TsiV3丧失了抑制活性,表明TsiV3的二聚化对于其发挥免疫蛋白的作用是必须的。该研究工作揭示了霍乱弧菌关键免疫蛋白行驶免疫保护功能的结构基础,为霍乱弧菌的防治提供了新靶点和新策略。(生物谷Bioon.com)

生物谷推荐的英文摘要:

Acta Cryst. (2014). D70, 1094-1103     doi:10.1107/S1399004714001242

Molecular mechanism for self-protection against the type VI secretion system in Vibrio cholerae

X. Yang, M. Xu, Y. Wang, P. Xia, S. Wang, B. Ye, L. Tong, T. Jiang and Z. Fan

VgrG proteins form the spike of the type VI secretion system (T6SS) syringe-like complex. VgrG3 of Vibrio cholerae degrades the peptidoglycan cell wall of rival bacteria via its C-terminal region (VgrG3C) through its muramidase activity. VgrG3C consists of a peptidoglycan-binding domain (VgrG3CPGB) and a putative catalytic domain (VgrG3CCD), and its activity can be inhibited by its immunity protein partner TsiV3. Here, the crystal structure of V. cholerae VgrG3CCD in complex with TsiV3 is presented at 2.3 ? resolution. VgrG3CCD adopts a chitosanase fold. A dimer of TsiV3 is bound in the deep active-site groove of VgrG3CCD, occluding substrate binding and distorting the conformation of the catalytic dyad. Gln91 and Arg92 of TsiV3 are located in the centre of the interface and are important for recognition of VgrG3C. Mutation of these residues destabilized the complex and abolished the inhibitory activity of TsiV3 against VgrG3C toxicity in cells. Disruption of TsiV3 dimerization also weakened the complex and impaired the inhibitory activity. These structural, biochemical and functional data define the molecular mechanism underlying the self-protection of V. cholerae and expand the understanding of the role of T6SS in bacterial competition.

 

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