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结构上不同的病毒抑制剂汇聚在一个共享的机制上,以阻断抗原转运器TAP的运行
James Lee1,2, Victor Manon1,2,3, Jue Chen1,2
1Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, NY 10065.
概括
诸如疹病毒和病毒之类的病毒使用蛋白质来阻断与抗原处理 (TAP) 相关的载体,从而隐藏感染细胞不受免疫检测. 这项研究揭示了四种病毒TAP抑制剂的结构,显示出一种常见的策略来禁用TAP并逃避免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 主体-病原体相互作用涉及病毒策略,以逃避免疫监测.
- 疹病毒和疹病毒编码的蛋白质抑制与抗原处理 (TAP) 相关的载体.
- TAP对于MHC-I抗原呈现至关重要,它向细胞毒性T细胞呈现病毒.
研究的目的:
- 为了结构性地描述剩余的四种已知的病毒TAP抑制剂.
- 为了组装一个全面的结构图谱病毒策略的TAP规避.
- 了解病毒用来抑制抗原呈现的常见机制.
主要方法:
- *使用冷电子显微镜 (cryo-EM) 来确定TAP的结构,并与四种病毒抑制剂复合.
- 对已知的五种病毒TAP抑制剂进行比较结构分析,包括之前已解决的HSV ICP47.7.
主要成果:
- *确定了与BNLF2a (EBV),hUS6 (CMV),bUL49.5 (BHV-1) 和CPXV012 (CPXV) 复合的TAP结构.
- 这些病毒抑制剂,尽管序列和结构多样性,共享一个共同的机制停滞TAP的交替访问周期.
- 这种抑制阻止了转移到ER,从而阻止了MHC-I呈现.
结论:
- * 病毒TAP抑制剂汇聚在一个保留的策略中,以破坏抗原的处理和呈现.
- 这些结构性见解为设计针对TAP抑制的新型抗病毒疗法提供了框架.
- 了解这些逃避机制是对抗终身病毒感染的关键.
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