T9SS PorKN环复合体的结构显示出基于重新设计的FGE折叠的形状可塑性
Xiangan Liu1, John D Perpich2, Liqiang Song1
1Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA.
mBio
|August 7, 2025
概括
解决了第九类分泌系统 (T9SS) 的结构,揭示了其分子结构和动态机制. 这为细菌蛋白质分泌和潜在的抗微生物点提供了洞察力.
科学领域:
- 结构生物学是结构生物学.
- 微生物学 微生物学
- 蛋白质分泌的分子机制
背景情况:
- 第九类分泌系统 (T9SS) 对于某些细菌类是独一无二的,对于毒性和运动性至关重要.
- T9SS机械包括PorLM电机,PorKN环和Sov转位器,但PorKN环的结构是未知的.
- Porphyromonas gingivalis 使用T9SS分泌超过30种毒性因子,导致牙周病.
研究的目的:
- 确定来自 Porphyromonas gingivalis 的 PorKN 环复合体的高分辨率冷电子显微镜 (EM) 结构.
- 为了阐明T9SS PorKN环的分子架构,组装和动态行为.
- 了解PorKN环与PorLM电机之间的相互作用.
主要方法:
- 低温电子显微镜 (EM) 以3.2 Å分辨率确定PorKN环复合体的结构.
- 在现场冷电子断层扫描以研究其本土环境中的复杂物.
- AlphaFold建模和位点定向的二硫化物交叉链接,以确定蛋白质与蛋白质之间的相互作用.
主要成果:
- PorKN 环结构显示出 33 倍的对称性,PorK 呈现出一种重新定位的甲基甘氨酸生成酶类折叠.
- PorK和PorN形成密集的子环,PorN中没有特征的螺旋对于复杂的稳定性至关重要.
- PorKN 环表现出形状的灵活性和可塑性,这表明基质运输过程中的动态变化.
- 确定了PorLM电机与PorKN环之间的接触,将电机与分泌装置连接起来.
结论:
- 该研究提供了T9SS PorKN环的第一个原子分辨率结构,揭示了其复杂的分子架构.
- 对PorKN环的动态行为和形状变化的洞察力为基板运输提供了一个建议的机制.
- 这些发现促进了对细菌蛋白质分泌的理解,并为开发针对P. gingivalis等病原体的新型抗菌战略提供了结构基础.
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