细菌的陪伴者CsgC通过促进内在无序的核前状态来抑制功能性粉样CsgA的形成
Anthony Balistreri1, Divya Kolli1, Sanduni Wasana Jayaweera2
1Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
The Journal of biological chemistry
|May 10, 2025
概括
陪伴蛋白CsgC在多个阶段抑制了大肠杆菌curli的amyloid形成. 它与前纤维CsgA和粉样纤维相互作用,减缓生长并充当能量独立的陪伴者.
科学领域:
- 微生物学 微生物学
- 生物化学 生化学
- 结构生物学 结构生物学
背景情况:
- 大肠杆菌 (Escherichia coli) 形成状粉样纤维,对生物膜发育至关重要.
- 主要的曲线子单元CsgA聚合成富含β片的结构.
- CsgC充当伴侣,抑制CsgA粉样蛋白的形成,但其精确的抑制机制尚不清楚.
研究的目的:
- 研究CsgC对CsgA粉样蛋白形成的阶段特异性抑制机制.
- 描述不同聚合状态下的大肠杆菌CsgC和CsgA之间的相互作用.
- 探索来自其他细菌物种的CsgC同类的抑制潜力.
主要方法:
- 纯化和CsgC同类的表征.
- 在体外粉样蛋白形成测试中监测滞后阶段和延长.
- 离子移动性质谱测试用于检测CsgC-CsgA相互作用.
- 对CsgC对预制CsgA种子和纤维的影响分析.
主要成果:
- 来自Citrobacter youngae,Cedecea davisae和Hafnia alvei的CsgC同类物都延长了大肠杆菌CsgA粉样蛋白形成的滞后阶段.
- 大肠杆菌CsgC与单体,前核CsgA暂时相互作用,延迟了核形成.
- CsgC抑制了CsgA聚合的指数增长,并与CsgA纤维相互作用,阻碍了延长.
结论:
- 通过多阶段干扰,CsgC抑制了状粉样蛋白的形成,对早期核化和晚期延长阶段都起作用.
- CsgC作为一种能量独立的伴侣作用,与前纤维素CsgA暂时相互作用,与成熟的粉样纤维更稳定地相互作用.
- 这些发现阐明了CsgC在曲线生物发生中的复杂调节作用.
关键词:
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