酶3/7调节的气体皮质E激活的分子机制和进化差异
Hang Xu1,2,3, Zihao Yuan1,2, Kunpeng Qin1,2,3
1CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology; CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.
eLife
|March 15, 2024
概括
由于CASP7中的一个关键残留物,Caspase-7 (CASP7) 基质对气体皮质E (GSDME) 的特异性因物种而异. 这解释了为什么一些GSDME被CASP7分裂,而另一些则没有.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 体酶 (CASP) 是激活气体皮质胺 (GSDM) 执行热的蛋白酶.
- 人类CASP3和CASP7在气体皮质E (GSDME) 中识别了相同的DxxD图案,但只有CASP3可以切割人类GSDME.
研究的目的:
- 阐明CASP7对GSDME的基质歧视背后的分子机制.
- 为了研究在脊椎动物中CASP3/7-介导的GSDME激活的进化分歧.
主要方法:
- 识别和特征气泡鱼GSDME及其与CASP3/7.7的相互作用.
- 在鱼和人类CASP和GSDME之间利用域交换实验.
- 在CASP7 p10子单元和GSDME C-terminus中分析了关键残留物.
主要成果:
- 气泡鱼GSDME是由气泡鱼和人类CASP3/7.2分离的.
- GSDME C端和CASP7 p10亚单元的关键残留物决定了GSDME的可裂性通过CASP7.
- 在CASP7中保存的关键残留物控制了基质歧视,哺乳动物的变异影响了GSDME裂变.
结论:
- 揭示了GSDME裂变中CASP7基质特异性的分子基础.
- 证明了CASP3/7-GSDME相互作用的进化差异,特别是在哺乳动物中.
- 建议CASP突变驱动细胞过程调节的功能专业化.
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