收费类受体4路径的进化轨迹和功能出现
Shailya Verma1, Ramanathan Sowdhamini1,2,3
1National Centre for Biological Sciences (TIFR), Bangalore, India.
Frontiers in immunology
|February 4, 2025
概括
收费类受体4 (TLR4) 信号传递涉及TRAM和TRIF蛋白质. 虽然关键残留物保留在祖先物种Callorhincus milli中,但TRAM信号残留物并非如此,这表明TLR4功能逐渐演变.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
背景情况:
- 收费类受体4 (TLR4) 识别细菌脂多糖 (LPS),通过TIRAP-MyD88或TRAM-TRIF信号通路启动细胞因子的产生.
- TRAM-TRIF路径在很大程度上是TLR4的特异性,而TIRAP-MyD88路径则是其他TLR的共同性.
- 之前的研究确定了Callorhincus milli作为一种拥有TRAM和TRIF蛋白质的祖先生物.
研究的目的:
- 研究TRAM和TRIF TIR领域在TLR4信号传输中的进化保护和功能意义.
- 为了比较TRAM-TRIF复杂结构和祖先Callorhincus milli和Homo sapiens之间的能量.
主要方法:
- 从跨种类的代表性生物中对TRAM-TRIF复合物的分子建模.
- 计算相互作用表面,能量和静电潜力.
- 正常模式分析 (NMA) 和分子动力学模拟以确定功能重要残留物和网络参数.
主要成果:
- 四重体TRAM-TRIF复合物 (TRAM二次体和TRIF二次体) 显示出比三重体模型更大的稳定性.
- 维护了TIRAP,TRIF和MyD88信号的关键残留物.
- 对于TRAM信号传输至关重要的关键残留物被发现在Callorhincus milli.中没有保存.
结论:
- 这些发现表明,在祖先的Callorhincus milli.中存在功能TIRAP-MyD88介导的TLR4和TRIF介导的TLR3信号.
- 显然,TLR4信号传递的进化涉及通过在进化时间内的多个动机的编排来逐渐获得功能.
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