与抗原处理相关的载体直接输出核酸依赖的构造变化
James Lee1, Victor Manon2, Jue Chen3
1Laboratory of Membrane Biophysics and Biology, the Rockefeller University, New York, NY 10065, USA.
Immunity
|August 30, 2025
概括
与抗原处理相关的载体 (TAP) 将转移到内网络中进行免疫反应. 克里奥EM结构揭示了TAP如何改变形状以运输和释放,防止ER压力.
科学领域:
- 分子生物学
- 免疫学
- 结构生物学
背景情况:
- 与抗原处理 (TAP) 相关的载体对适应性免疫至关重要.
- TAP促进了抗原从细胞质到内细胞质网膜 (ER) 的运输.
- 这一过程对于将载入主要组织相容性复合物I类 (MHC-I) 分子至关重要.
研究的目的:
- 阐明人类TAP异构体对的运输和释放的结构机制.
- 了解TAP在整个运输周期中的功能状态.
- 提供一个结构性的基础,
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定高分辨率结构.
- 在多个功能状态下捕获人类TAP异构体的结构.
- 分析的重点是与ATP结合和水解相关的形状变化.
主要成果:
- 解决了TAP的明显向内和向外的形状.
- ATP结合稳定了面向内部的状态,使腔暴露在细胞质中.
- 过渡到面向外的状态将重新配置用于ER光道释放的结位.
- ATP水解和核酸结合域分离驱动输送循环并重置输送器.
结论:
- 已经建立了TAP介导运输的综合结构框架.
- 这些发现解释了单边转移和释放的机制.
- 这项研究揭示了转抑制的结构基础,这是防止ER压力的反机制.
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