Fusobacterium nucleatum adhesin与癌症和免疫细胞上的受体相互作用的结构基础
Felix Schöpf1,2, Gian L Marongiu1,2, Klaudia Milaj1,3
1Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Nature communications
|August 29, 2025
概括
杆菌核
科学领域:
- 微生物学
- 结构生物学
- 癌症研究
背景情况:
- 核菌与结直肠癌的进展和转移有关.
- F.核素的Fap2粘附蛋白与癌症和免疫细胞的相互作用中介.
- 在免疫细胞上Fap2与TIGIT结合的确切机制尚不清楚.
研究的目的:
- 阐明Fap-TIGIT相互作用的结构基础.
- 描述Fap2与癌细胞受体 (Gal-GalNAc) 和免疫细胞受体 (TIGIT) 的结合.
主要方法:
- 在大肠杆菌表面的功能Fap2的重组表达.
- 电子显微镜 (Cryo-EM) 用于结构的确定.
- 结构预测,对接和分子动力学模拟.
主要成果:
- 在大肠杆菌表达的功能Fap2具有高亲和力结合Gal-GalNAc和TIGIT.
- 化EM显示Fap2的50nm细胞外区域将TIGIT与其膜-远端结合在一起.
- 在Fap2尖端确定了Gal-GalNAc的特定结合部位.
结论:
- 对Fap2-TIGIT相互作用的结构洞察力提供了机理性的理解.
- Fap2在其TIGIT交互尖端使用了不同的Gal-GalNAc结合孔.
- 这项研究为在结直肠癌治疗中准Fap2奠定了基础.
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