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人类GBP1防御复合体的原生架构,用于细胞自主免疫

Shiwei Zhu^1,2,3,4, Clinton J Bradfield^1,2,3,4, Agnieszka Maminska^1,2,3,4

¹Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.

Science (New York, N.Y.)

|February 29, 2024

概括

人类细胞使用酸结合蛋白 (GBPs) 形成一个巨大的纳米机器,以抵御阴性细菌. 这种复合物激活免疫信号和细胞死亡途径以消除感染.

科学领域:

细胞生物学
免疫学
结构生物学

背景情况:

生物体拥有细胞自主防御对病原体.
超分子复合体是植物和动物免疫反应的关键.
格拉姆阴性细菌是一个严重的传染性威胁.

研究的目的:

解决一个巨大的宿主防御复合体的原生结构,
在人类细胞中阐明这个纳米机器的组装和功能.

主要方法:

使用冷电子断层扫描来确定复合物的结构.
生物化学试验用于研究复杂的组装和功能.
进行了关三酸盐水解和蛋白质招募的分析.

主要成果:

在细菌表面观察到大约30,000个酸结合蛋白 (GBPs) 的聚合物.
复杂的形成需要三酸盐水解,并招募caspase-4和Gasdermin D.
GBP1的扩展形状促进了细菌膜的插入和脂多糖的释放,激活了caspase-4.

结论:

人类的GBP1防御复合体形成了一个动态的纳米机器,用于对抗带阴性细菌的先天免疫力.
这种复合物作为细胞因子和细胞死亡信号的平台.
"开放型"模型提供了对GBP1抗感染机制的见解.

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