通过三元体自传递体粘附素CbpF的Fusobacterium nucleatum通过免疫细胞结合的结构基础
Gian Luca Marongiu1, Uwe Fink1, Felix Schöpf1
1Leibniz-Forschungsinstitut fur Molekulare Pharmakologie, Berlin 13125, Germany.
概括
杆菌核酸 (Fusobacterium nucleatum) 是一种细菌
科学领域:
- 微生物学和结构生物学
背景情况:
- 菌核素 (Fn) 与结直肠癌 (CRC) 的进展和免疫逃避有关.
- 粘性CbpF向T细胞上的CEACAM1,有助于瘤免疫逃避.
- 在此之前,CbpF-CEACAM1相互作用的结构基础是未知的.
研究的目的:
- 为了确定Fusobacterium核素CbpF粘合物的高分辨率结构.
- 阐明CbpF与宿主受体CEACAM1.1结合的结构机制.
- 为开发针对结直肠癌Fn的向治疗提供见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 和单颗粒分析来获得结构.
- 使用表面等离子体共振 (SPR) 来确定结合亲和力.
主要成果:
- 解决了两个结构:单独CbpF和CbpF与CEACAM1.1复合在一起.
- CbpF形成了一个稳定的同位三元复合体,具有独特的细胞外β-滚域.
- CEACAM1以高亲和度 (纳米分离常数) 与CbpF的β-滚域上的侧环结合.
结论:
- 这项研究提供了第一个全面的结构描述的fusobacterial三元体自传递粘附素 (TAA).
- 通过CbpF的侧环介导的新型CEACAM1结合模式被揭示出来.
- 这些发现为合理的药物设计奠定了基础,针对Fn在结直肠癌治疗中.
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