通过apoptotic蛋白酶激活因子1的procaspase-9招募的结构基础
1Department of Chemistry, Princeton University, New Jersey 08544, USA.
Nature
|June 22, 1999
概括
细胞亡是由caspase-9调节的,该酶由Apaf-1激活. 结构分析揭示了对于这种caspase-9激活过程及其在其他生物体中的保存至关重要的特定分子相互作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 卡斯巴-9介导的亡对于多细胞生物的发育和恒温至关重要.
- 成熟的caspase-9是由其procaspase前体通过Apaf-1的招募生成的.
研究的目的:
- 为了阐明Apaf-1和procaspase-9相互作用的结构基础.
- 了解酶-9激活特异性背后的分子机制.
主要方法:
- 进行X射线晶体学以确定Apaf-1的caspase-recruitment域及其与procaspase-9原域复合的结构.
- 位点定向突变发生,以调查接口残留的作用.
- 无细胞系统用于评估procaspase-9激活.
- 在Caenorhabditis elegans.中对同类的比较分析.
主要成果:
- 晶体结构揭示了两个充电的,互补的表面,通过键和范德瓦尔斯力调解Apaf-1和procaspase-9的相互作用.
- 关键接口残留物中的突变使得在体外 (in vitro) 激活 prokaspase-9 的功能受损.
- 野生类型的原原体抑制了公酶-9处理,而突变体没有.
- 同类分析表明,保存的结构动机介于CED-4对CED-3的招聘.
结论:
- 对于精确的激活,Apaf-1和procaspase-9之间的特定分子间相互作用至关重要.
- 这些相互作用机制在物种中得到保护,突出了它们的基本生物学重要性.
相关概念视频
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01:24Caspases
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01:17The Extrinsic Apoptotic Pathway
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