在1型 pili中,外膜导体对粘附分泌的结构基础是1型 pili
Ryan M Bitter1, Maxwell I Zimmerman2,3, Brock T Summers4
1Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110.
概括
格拉姆阴性细菌使用伴侣-usher pili进行宿主相互作用. 这项研究揭示了粘附蛋白FimH如何改变形状,通过介面孔转移,这对于柱子组装和感染至关重要.
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 生化学
背景情况:
- 陪伴者路径的 pili 是关键的毒性因素,在格拉姆阴性细菌.
- 这些 pili通过特定的粘合素结合来调解宿主-病原体相互作用和组织热带性.
- 通过保证孔穿过外膜的粘附蛋白转移的机制尚未完全理解.
研究的目的:
- 阐明粘合物通过外膜转移的结构机制.
- 研究结构性可塑性在柱体生物发生和功能中的作用.
- 为FimH提供分子洞察力,以及与尿路感染相关的Usher动态.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定四元尖端复合体 (FimD,FimC,FimH,FimF) 的结构.
- 生物化学试验,包括化试验,以评估结构发现的功能意义.
- 在转位过程中对粘合物的不同状态进行比较结构分析.
主要成果:
- 一个冷-EM结构捕获了FimD分泌粘合物FimH的带领者,揭示了一个独特的中间状态.
- 两个域粘合物FimH在转位过程中表现出显著的结构可塑性.
- 灵活的FimH域之间的连接器使这种可塑性成为可能,这对于Usher转移和柱子组装至关重要.
结论:
- 粘合物的结构性可塑性是通过保手孔转移的先决条件.
- 这项研究提供了前所未有的分子细节,介绍了穿过外膜的粘合素分泌.
- 了解这些动态对于开发针对格拉姆阴性细菌感染的新疗法至关重要,包括尿路感染.
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