DELE1的寡合化促进了综合应激反应的激活
Jie Yang1, Kelsey R Baron2, Daniel E Pride1
1Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
Nature structural & molecular biology
|August 7, 2023
概括
线粒体应激触发DELE1释放,启动综合应激反应 (ISR) 信号传递. 低温EM显示,DELE1形成了HRI激酶激活和细胞应激反应必不可少的八度体.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 线粒体是细胞应激反应的关键调节者.
- 线粒体应激信号涉及DELE1和综合应激反应 (ISR).
- 在DELE1片段激活eIF2α激酶HRI.
研究的目的:
- 为了确定DELE1寡合体的结构.
- 阐明DELE1介导的ISR激活的分子机制.
- 为了确定涉及DELE1寡合化和功能的关键残留物.
主要方法:
- 电子显微镜 (cryo-EM) 用于结构的确定.
- 突变性研究,以评估关键残留物的作用.
- 细胞培养模型用于评估ISR激活.
主要成果:
- 人类DELE1的C端片段形成了一个稳定的D4对称八位数.
- 特定的疏水性相互作用调解了DELE1单体组合到八合体中.
- 破坏DELE1寡合化的突变取消了依赖HRI的ISR激活.
结论:
- 对于其传递线粒体压力信号的功能来说,DELE1的寡合化是至关重要的.
- 八米基结构为DELE1在ISR中的作用提供了分子洞察力.
- DELE1组件对于激活HRI和促进细胞适应线粒体损伤至关重要.
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