托尔类受体8二元体的结构重组,由激动性联结体诱导
Hiromi Tanji1, Umeharu Ohto, Takuma Shibata
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
概括
通过连接体激活托尔类受体8 (TLR8) 的结构性特征. 带结合会诱导TLR8二元重组,从而使下游的先天免疫信号传递成为可能.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 收费类受体7 (TLR7) 和收费类受体8 (TLR8) 是参与先天免疫的关键模式识别受体.
- 这些受体识别单链RNA并启动免疫反应.
- 针对TLR7-TLR8的合成激动剂显示出治疗前景,但连接体识别和激活的分子机制尚不清楚.
研究的目的:
- 阐明连接体识别和激活人类托尔类受体8 (TLR8) 的分子基础.
- 确定TLR8在带结合时的结构变化及其在信号传递中的作用.
主要方法:
- 确定了人类TLR8二元体的无结合和结合结合的晶体结构.
- 在刺激后对TLR8二元体的结构重组的分析.
主要成果:
- 连接体识别发生在由两个TLR8原体形成的二元化接口上.
- 干结合诱导TLR8二元体的显著重组,使C末端相邻.
- 观察到白丰富的重复14 (LRR14) 和LRR15之间的循环裂变,与N和C终端半端保持关联.
结论:
- 干结合触发了TLR8二元体的构造变化,促进了下游的信号传输.
- 结构重组对于通过TLR8.8调解的先天免疫反应的激活至关重要.
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