结构和功能洞察力对调节T细胞的T细胞共刺激由麻疹病毒蛋白M2的调节
Shangyu Yang1, Yong Wang2,3, Feiyang Yu1
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Nature communications
|August 25, 2023
概括
病毒病毒M2蛋白与人类B7.1/2结合,阻断T细胞的激活. 这揭示了病毒免疫逃避的关键机制,并提供了对病毒 (MPXV) 病原体的见解.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 病毒 (MPXV) 构成了全球健康威胁.
- 毒病毒M2蛋白通过调节宿主反应,对免疫逃避至关重要.
- 尚不清楚MPXV M2与B7配体的精确相互作用及其结构基础.
研究的目的:
- 阐明MPXV M2蛋白与人类B7.1/2.2之间的相互作用.
- 确定MPXV M2免疫逃避功能的结构基础.
主要方法:
- 该研究使用冷电子显微镜 (Cryo-EM) 来确定结构.
- 生物化学测试被用来评估结合 afinities 和相互作用.
主要成果:
- MPXV M2存在于六合体和六合体,识别人类的B7.1和B7.2 (hB7.1/2) 具有很高的热情.
- 寡合MPXV M2结合破坏了hB7.1/2与CD28和CTLA4.4的相互作用.
- 低温-EM结构显示MPXV M2与hB7.1/2结合,在固体上阻碍CD28和CTLA4结合并颠覆T细胞激活.
结论:
- MPXV M2采用固体竞争机制来逃避宿主免疫力.
- 对MPXV M2-hB7.1/2相互作用的结构洞察力解释了毒病毒免疫逃避策略.
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