pH-天线残留触发了人类CD81受体的大细胞外循环领域的大规模结构变化
C Risueño1,2, I Carbajo3,4, D Charro1
1Structure and Cell Biology of Viruses Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain.
The Journal of chemical physics
|April 16, 2025
概括
CD81大细胞外循环域 (CD81LEL) 的可塑性是由天线残留物D139和E188.8控制的. 这些残留物调节溶解,驱动pH值依赖的形状变化,从封闭状态到开放状态.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 分子细胞生物学 分子细胞生物学
背景情况:
- CD81是一种参与细胞信号传递的人类受体.
- 建议CD81大细胞外环域 (CD81LEL) 形状依赖于pH值.
- CD81LEL可塑性的确切机制仍未得到证实.
研究的目的:
- 阐明CD81LEL中依赖pH的形状变化的机制.
- 为了确定负责CD81LEL可塑性的关键残留物.
- 为了研究溶解调制在CD81LEL形状转换中的作用.
主要方法:
- 分子动力学模拟.分子动力学模拟.
- 在CD81LEL.上进行光谱实验.
- 关键残留物 (D139和E188) 的位点定向突变发生.
主要成果:
- CD81LEL的pH依赖性开口是由天线残留物D139和E188.8介导的.
- 这些残留物改变了溶解,触发了改变形状的信号级联.
- 致使D139和E188的pH敏感性失效的突变稳定了CD81LEL的封闭形状.
结论:
- 揭示了CD81LEL可塑性的新机制,涉及天线残留物和溶解调制.
- 在CD81LEL中,D139和E188对于pH诱导的形状转变至关重要.
- 这种信号转导机制可能与内体通路中的其他受体有关.
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