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鼠标RIPK1的结构含有RHIM的域作为homo-amyloid和RIPK1/RIPK3复合体中的结构

Jing Liu^1,2, Xia-Lian Wu², Jing Zhang¹

¹School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

Nature communications

|August 14, 2024

概括

受体相互作用蛋白激酶1 (RIPK1) 形成粉样结构,对细胞亡至关重要. 这项研究揭示了RIPK1.

科学领域:

生物化学生化学
结构生物学结构生物学
细胞生物学细胞生物学

背景情况:

受体相互作用蛋白激酶1 (RIPK1) 是神经退行性疾病和癌症的关键治疗点.
RIPK1的中心域包含一个受体相互作用蛋白同型相互作用动机 (RHIM),它调解了粉样蛋白的形成.
由RIPK1和RIPK3形成的功能性粉样蛋白调节编程细胞死亡 (亡).

研究的目的:

为了确定小鼠RIPK1.1.的粉样蛋白结构.
为了研究RIPK1和RIPK3粉样蛋白之间的结构差异.
了解RIPK1/RIPK3相互作用在死调节中的作用.

主要方法:

固态核磁共振 (NMR) 光谱学. 固态核磁共振 (NMR) 光谱学.
一个以RHIM域为中心的82-残留小鼠RIPK1序列的结构分析.

主要成果:

这项研究介绍了小鼠RIPK1的粉样结构,揭示了具有四个β链的"N"形子单元折叠.
这种折叠模式,以保存的I/VQI/VG四为特征,在含有RHIM的蛋白质中是共享的.
固态NMR发现小鼠RIPK1和RIPK3之间的结构差异,混合纤维中的RIPK3信号减弱.

结论:

这些发现为RIPK1和RIPK3粉样蛋白形成的结构基础提供了关键的见解.
了解这些RHIM介导的相互作用对于破译亡调节机制至关重要.
这些结构信息可以指导针对涉及RIPK1的疾病开发有针对性的治疗方法.

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