一个histidine开关通过caspase-9 CARD调节pH依赖的光纤形成
bioRxiv : the preprint server for biology
|June 12, 2025
概括
卡斯帕-9 CARD 蛋白自组装成纤维,这对于细胞信号传递至关重要. 它的聚合取决于pH值,受到一个关键的胺残留物 (H38) 的影响.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 酶激活和招募域 (CARD) 调解了亡和炎症中的蛋白质相互作用.
- 超过30种人类蛋白质含有CARDs,其中一些形成螺旋丝.
研究的目的:
- 研究caspase-9 CARD (C9 CARD) 自身组装成纤维的过程.
- 阐明静电相互作用和pH在C9 CARD聚合中的作用.
主要方法:
- 在体外聚合试验.
- 核磁共振 (NMR) 光谱测定胺pKa.
- 电子显微镜 (cryo-EM) 用于结构的确定.
主要成果:
- C9 卡片在生理条件下自组装成丝.
- 在低盐或酸性条件下,聚合物增强,表明静电参与.
- 正如突变研究 (H38R,H38D,H38N) 所显示的那样,histidine 38 (H38) 质子化对线索形成至关重要.
- 冷电磁结构揭示了野生型和H38R C9 CARD纤维的原子细节.
结论:
- C9 CARD的聚合受pH值通过histidine 38.显著影响.
- 对C9 CARD丝形成的结构洞察力为了解其在信号通路中的作用提供了基础.
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