TFPI是来自高病毒性C. difficile的TcdB的结肠密码受体
Jianhua Luo1, Qi Yang1, Xiaofeng Zhang2
1Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang 310024, China.
Cell
|March 18, 2022
概括
高病毒性Clostridioides difficile菌株使用组织因子通路抑制剂 (TFPI) 作为受体. 这一发现显示TFPI是TcdB的结肠密码受体,为C. difficile感染的发病提供了新的见解.
科学领域:
- 微生物学
- 分子生物学
- 结构生物学
背景情况:
- 过度病毒性类型2 Clostridioides difficile菌株引起严重的感染,其中TcdB是关键的毒性因子.
- 克莱德2菌株表达TcdB变体 (TcdB2,TcdB4),与经典TcdB不同,与未知的受体结合.
研究的目的:
- 从高病毒性C. difficile类2菌株中识别TcdB4的受体
- 阐明TcdB受体相互作用的结构基础及其在致病过程中的作用.
主要方法:
- 通过CRISPR/Cas9查识别TcdB4受体.
- 用冷电子显微镜 (cryo-EM) 确定TcdB4-TFPI复合物的结构.
- 对TcdB变体受体结合区域的分析.
主要成果:
- 组织因子通路抑制剂 (TFPI) 被确定为TcdB4的受体.
- 克里奥EM揭示了TcdB4-TFPI复合体的结构,定义了一个共同的TcdB受体结合区域.
- 该区域根据受体偏好将TcdB变异分为两组:Frizzled (FZD) 或TFPI.
- TFPI在肠道腺体中表达很高,并保护结肠上皮从TcdB2/4中.
结论:
- 已确定TFPI是2类C. difficile的TcdB的结肠密码受体.
- 这些发现揭示了Clostridioides difficile感染 (CDI) 病变的新机制.
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