BoNT/Wo-NTNH复合体的冷-EM结构显示了两个类似免疫球蛋白的域
Sara Košenina1, Jana Škerlová1,2, Sicai Zhang3,4,5
1Department of Biochemistry and Biophysics, Stockholm University, Sweden.
The FEBS journal
|September 25, 2023
概括
来自Weissella oryzae (BoNT/Wo) 的类似肉毒神经毒素的毒素与其合作伙伴蛋白质形成一个复合体. 它独特的结构表明了激活和宿主细胞相互作用的新机制.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 肉毒神经毒素 (BoNTs) 通常是由克洛斯特里迪亚物种产生的.
- 为了稳定性,BoNTs与无毒的非血凝素 (NTNH) 蛋白质形成复合体.
- 在Clostridium属之外,已经确定了类似BoNT的毒素,包括来自Weissella oryzae (BoNT/Wo).
研究的目的:
- 为了确定BoNT/Wo-NTNH/Wo复合物的冷电子显微镜 (cryo-EM) 结构.
- 为了研究BoNT/Wo-NTNH/Wo复合物的pH稳定性.
- 阐明BoNT/Wo和NTNH/Wo之间的相互作用的结构基础.
主要方法:
- 电子显微镜 (cryo-EM) 用于结构的确定.
- 测试pH稳定性. 测试pH稳定性.
- 质量摄影分析.
主要成果:
- 确定了300kDa的BoNT/Wo-NTNH/Wo复合结构,揭示了毒素与伴侣相互作用的分子细节.
- NTNH/Wo具有两个独特的C端细菌免疫球蛋白类 (Big) 域,可能参与宿主细胞粘附.
- BoNT/Wo含有其他BoNT中缺少的内部二硫化物键.
- 该复合物在酸性条件下稳定,但在中性到基本的pH下解离.
结论:
- BoNT/Wo-NTNH/Wo共享了正规的BoNT-NTNH复合体的一般折叠.
- 独特的结构特征表明BoNT/Wo激活,转位和宿主细胞识别的替代机制.
- 需要进一步的研究来了解BoNT/Wo的活性,机制,点和受体.
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