膜结合蛋白质降解组件的结构可塑性支持细菌适应压力的适应
Naseer Iqbal1, Sandro Keller2,3,4, Alireza Ghanbarpour1
1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis.
bioRxiv : the preprint server for biology
|August 8, 2025
概括
像FtsH这样的细菌AAA+蛋白酶,与HflK/C蛋白质复合,对于适应抗生素压力至关重要. 这项研究揭示了HflK/C构成和FtsH相互作用是如何在氨基糖化物压力下对细菌生存至关重要的.
科学领域:
- 分子生物学分子生物学
- 结构生物学是结构生物学.
- 微生物学 微生物学
背景情况:
- 包括FtsH在内的AAA+蛋白酶对于细菌应激适应至关重要.
- 在内膜中,FtsH与SPFH家族蛋白HflK和HflC形成复合体.
- HflK/C存在于开放式和闭合式构造,影响FtsH蛋白酶活性.
研究的目的:
- 为了确定HflK/C复合物的生物活性构造.
- 研究HflK/C构成和FtsH相互作用在细菌对氨基糖化物应激反应中的作用.
主要方法:
- 设计了一种二硫化物交叉连接的HflK/C变体,以稳定封闭形状.
- 使用冷电子显微镜 (cryo-EM) 解决了稳定复合物的结构.
- 进行了表型测定,以评估在氨基糖化物应激下细菌生长.
主要成果:
- 稳定HflK/C在封闭形状中或破坏FtsH相互作用会在压力下损害细菌的生长.
- 低温EM揭示了在托布拉米应激下FtsH•HflK/C复合体中的一种新的HflK/C安排,具有用于基质访问的开口.
- 动态的HflK/C形状和特定的FtsH相互作用都对适应至关重要.
结论:
- HflK/C的动态性质及其与FtsH的相互作用对于细菌适应氨基糖化物诱导的压力至关重要.
- 这些发现为SPFH蛋白在细菌应激反应中的更广泛功能提供了洞察力.
- 这项研究阐明了细菌抗生素耐药性和生存的机制.
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