腺酸环酶毒素RTX域遵循了一系列模板折叠机制,对毒素活性有影响
Guojun Chen1, Han Wang1, Ladislav Bumba2
1Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.
The Journal of biological chemistry
|August 11, 2023
概括
百日咳 Bordetella 的折叠腺酸环酶毒素-血解素 (CyaA) 遵循一个连续的,C-终端到N-终端的路径. 这种严格的系列,模板折叠机制对于CyaA是必不可少的.
科学领域:
- 分子生物学分子生物学
- 蛋白质折叠 蛋白质的折叠
- 细菌病原体的产生
背景情况:
- 腺酸环酶毒素-血解素 (CyaA) 的重复中毒素 (RTX) 域对于 Bordetella pertussis 的毒性至关重要.
- 对于CyaA的毒素活动来说,RTX域 (RD) 的依赖的折叠是必不可少的,但折叠信号的传输机制仍然不清楚.
研究的目的:
- 阐明CyaA RTX域的五个RTX块内折叠信号传输的分子机制.
- 了解序列折叠如何影响CyaA的整体结构和毒素活性.
主要方法:
- 使用单分子光学子来探测蛋白质折叠动态.
- 使用蛋白质工程技术来操纵RTX块.
- 进行了毒素活性测定,以将折叠与功能相关联.
主要成果:
- 展示了 RD 的层次,顺序折叠路径,从 C 终端 RTX-v 块开始,继续到 N 终端 RTX-i 块.
- 确定了一系列模板折叠机制,折叠信号从C端向N端单向传播.
- 表明任何RTX块的干扰都会展开N终端区域,并消除CyaA毒素的活性.
结论:
- CyaA RD的顺序,C-终端到N-终端折叠对于其结构完整性和毒性功能至关重要.
- 这一发现为CyaA分泌和折叠提供了关键的机制见解.
- 提供了潜在的目标,用于开发治疗方法来对抗Bordetella pertussis感染.
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