嵌入膜的人类T细胞受体-CD3复合体的静止状态和连接体结合状态
bioRxiv : the preprint server for biology
|September 4, 2023
概括
T细胞受体 (TCR) 的静止状态是一个封闭的,紧的结构,不像以前想象的那样是开放的. 干结合会诱导T淋巴细胞激活所必需的开放形状.
科学领域:
- 结构生物学是结构生物学.
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- T细胞受体 (TCR) 综合体对于T淋巴细胞激活至关重要.
- 之前在洗剂小粒中进行的结构研究表明,未结合的TCR-CD3复合体具有"开放和扩展"的形状.
- 在TCR中介信号传输的机制细节仍然不完全理解.
研究的目的:
- 为了确定未结合和与人类白细胞抗原 (HLA) 结合的人类TCR-CD3复合物的本地结构.
- 为了研究与TCR激活相关的形状变化.
- 阐明脂质环境在TCR结构和功能中的作用.
主要方法:
- 低温电子显微镜 (cryo-EM) 的TCR-CD3复合物复制成纳米光盘.
- 不同形状状态的结构分析.
- 生物化学试验使用结构锁定型二硫化物突变体.
主要成果:
- 纳米光盘中的未结合的TCR-CD3复合体采用"封闭和压缩"的构造,代表生理休息状态.
- 与HLA结合的TCR-CD3复合体采用"开放和延伸"的形状.
- 对TCR-CD3复合体的ectodomain开放对于最大的依赖连接体的T细胞激活至关重要.
结论:
- TCR激活涉及从封闭状态到开放状态的全形状变化.
- 原生类脂质环境对于准确的膜蛋白结构确定至关重要.
- 这些发现为T细胞激活的分子机制提供了新的见解.
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