人类DPP4受体被MERS类冠状病毒2014-422和GX2012识别的结构基础
Zichun Lin1,2,3, Teng Gao1,2, Xinquan Wang1,2,3
1Beijing Frontier Research Center for Biological Structure, Beijing, China.
PLoS pathogens
|January 7, 2026
概括
来自蝙蝠的两种新型MERS类型冠状病毒与人类的DPP4.4结合. 结构分析显示,由于额外的残留物,结合角度发生了变化,影响受体识别,并为Merbecovirus监测提供了洞察力.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 冠状病毒 冠状病毒
背景情况:
- 中东呼吸综合征冠状病毒 (MERS-CoV) 构成了严重的公共卫生威胁.
- 经常发现具有动物传染潜力的新型MERS类冠状病毒.
- 两种特定的蝙蝠冠状病毒菌株BatCoV/Ii/GD/2014-422 (2014-422) 和BtTp-BetaCoV/GX2012 (GX2012) 被分离并选择进行研究.
研究的目的:
- 确定两种新型蝙蝠冠状病毒的尖尖糖蛋白剪切器的冷电子显微镜 (cryo-EM) 结构.
- 为了研究它们与人类受体, dipeptidyl peptidase 4 (hDPP4) 的相互作用的结构基础.
- 了解它们潜在的跨物种传播潜在的分子机制.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定尖端糖蛋白剪切物的结构及其与hDPP4.4的复合体.
- 进行了生物化学测试,以确认病毒尖端蛋白与hDPP4.4的结合.
- 对复合体进行了详细的结构分析,以确定关键的相互作用残留物和结合模式.
主要成果:
- 与MERS-CoV.相比,冷-EM结构显示了尖端糖蛋白三元体的更紧的构造.
- 无论是2014-422和GX2012的尖端受体结合域 (RBDs) 都证明了与人类DPP4 (hDPP4) 的结合.
- 对RBD-hDPP4复合物的结构分析显示了保留的结合模式,但具有显著的倾斜角度,这归因于514位的额外残留物与hDPP4 N321糖相互作用.
结论:
- 这些发现为这些新型Merbecoviruses的受体利用提供了详细的结构洞察.
- 位置514的额外残留物在改变结合角度和影响受体识别方面发挥着至关重要的作用.
- 这项研究为加强对具有动物感染潜力的MERS类冠状病毒的监测提供了结构性基础.
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