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面膜蛋白通过诱导封闭形状并将其分离到生物分子凝聚物中使NF-κB前体保持不活跃

Kewei Zheng¹, Xiawei Huang¹, Xiaojiang Yang¹

¹State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

|September 5, 2025

概括

多重安基林重复单个KH域 (Mask) 蛋白通过形成凝结物来抑制先天免疫因子Relish. 在刺激时,Mask被裂开,释放Relish以产生免疫反应,这种机制在哺乳动物中部分保留.

科学领域:

* 分子和细胞生物学
* 免疫学
* 遗传学

背景情况:

* 核因子 κB (NF-κB) 转录因子对先天免疫至关重要,并且在疾病中经常受到调节.
作为研究免疫调节的模型,Relish是一种Drosophila NF-κB同源物.
* 维持NF-κB在静止状态中的机制尚未完全理解.

研究的目的:

* 为了识别Relish的新型调节剂,Drosophila NF-κB同源物.
* 阐明在没有免疫刺激的情况下控制Relish无活性的机制.
* 研究生物分子凝聚物的NF-κB通路调节作用.

主要方法:

* 蛋白与蛋白相互作用测试以确定Mask是一种Relish抑制剂.
* 聚焦显微镜可视化Mask-Relish相互作用和凝结物形成.
* 用Drosophila进行基因操纵,以研究Mask和DREDD的功能后果.
* 在体外裂解测定以确认DREDD在Mask调节中的作用.

主要成果:

* 多个ankyrin重复单个KH域 (Mask) 通过保持封闭的构造直接结合并抑制Relish.
* 面膜形成生物分子凝聚物,将Relish与激活酶,DREDD隔离.
* 免疫刺激触发了Mask与Relish的分离以及随后的DREDD分裂,激活了Relish.
* 面膜对NF-κB信号的抑制功能在哺乳动物系统中部分保留.

结论:

通过控制Relish的局部化和活性,Mask作为Drosophila NF-κB通路的关键抑制剂.
* 生物分子凝聚物形成是调节先天免疫信号的关键机制.
* 了解面膜调节提供了关于NF-κB稳态和潜在治疗点的见解.

关键词:

CP:免疫学 CP:分子生物学美国类植物国际海事指令通道在 NF-κB 生物分子凝结物天生的免疫力液态相隔离一个面具其他类型一个味道

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