Fas-FADD死亡域复杂结构通过受体聚类来解开信号
Fiona L Scott1, Boguslaw Stec, Cristina Pop
1Program in Apoptosis and Cell Death Research, The Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Nature
|January 2, 2009
概括
Fas受体和FADD的相互作用形成了一个关键的诱导死亡的信号复合体 (DISC) 亡. 结构分析揭示了一个调节性Fas-FADD复杂桥梁,作为编程细胞死亡的分子开关.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 诱导死亡的信号复合体 (DISC) 对于启动亡至关重要.
- DISC的形成依赖于Fas受体和FADD (Fas关联死亡域蛋白) 之间的相互作用.
- 缺乏关于Fas-FADD相互作用的结构数据,阻碍了机理学理解.
研究的目的:
- 描述DISC内部Fas-FADD相互作用的结构基础.
- 阐明DISC组装和调节的机制.
主要方法:
- 人类Fas-FADD死亡域综合体的形成和分离.
- 进行X射线晶体学以确定2.7 Å的晶体结构.
主要成果:
- 晶体结构显示出一个由四个FADD死亡域与四个Fas死亡域结合的四重复合体.
- Fas死亡域的开放暴露了FADD结合部位,形成了一个Fas-Fas桥梁.
- 一个调节性Fas-FADD复杂桥梁,由弱相互作用控制,作为一个分子开关.
结论:
- Fas-FADD复合体作为机械开关,防止过早的DISC组装,同时允许在刺激时有效形成.
- 这项研究揭示了一种新的死亡域相互作用模式,以及通过寡合化和集群的受体信号传递机制.
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