RIP1/RIP3体形成了一个功能性粉样体信号复合体,该复合体是编程体所需的
Jixi Li1, Thomas McQuade, Ansgar B Siemer
1Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Cell
|July 24, 2012
概括
RIP1和RIP3激酶形成粉样纤维,驱动程序化. 用诸如蒂奥夫拉T之类的染料抑制这些粉样蛋白结构,部分阻断了缩,揭示了新的信号机制.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 瘤亡因子 (TNF) 诱导的编程亡涉及RIP1和RIP3激酶.
- 控制RIP激酶信号的精确结构机制仍然不完全理解.
研究的目的:
- 为了研究 RIP1 和 RIP3 激酶复合体形成的结构基础.
- 确定 RIP 同型相互作用基因 (RHIM) 在酶组合和信号传递中的作用.
- 探索粉样蛋白结构在编程性亡中的潜在参与.
主要方法:
- 生物物理技术包括提奥夫拉T (ThT) 和刚果红色 (CR) 结合试验,循环二极化,红外光谱学,X射线衍射和固态NMR.
- 对RIP1和RIP3RHIM突变的分析.
- 从死细胞中分离并表征内源RIP1/RIP3复合体.
- 在体内对编程性亡的研究.
主要成果:
- 在RIP1和RIP3RHIM中,RHIM中介于异构体粉样纤维的形成.
- 这些纤维具有结构化的粉样核,并附带移动区域.
- 内生RIP1/RIP3复合体表现出粉样蛋白的特征,并且具有超稳定性.
- 粉样蛋白染料 (ThT,CR,HBX) 部分抑制了编程性缩.
- RHIM突变破坏了酶复合体的形成,激活和编程死亡.
结论:
- RIP 激酶组装成粉样蛋白结构,这些结构对编程性亡至关重要.
- 粉样蛋白形成是RIP激酶介导信号传递中的关键结构事件.
- 这项工作将已知的粉样蛋白的功能扩展到细胞信号复合体.
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