N-终端乙化保护蛋白质免受降解,并促进与年龄相关的运动性和寿命
Sylvia Varland1,2,3, Rui Duarte Silva4,5, Ine Kjosås6
1Department of Biomedicine, University of Bergen, N-5021, Bergen, Norway. sylvia.varland@gmail.com.
Nature communications
|October 27, 2023
概括
通过 NatC 的 N-终端乙化保护蛋白质免受降解. 这种与ubiquitin结合酶的关键相互作用影响寿命和运动性,突出显示了乙化作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 大多数真核蛋白经历N端乙化,但其广泛的功能意义在很大程度上仍未知.
- 了解N端乙化的调节和影响对于破译蛋白质稳态至关重要.
研究的目的:
- 在全基因组规模上研究N端乙化的功能后果.
- 阐明将N端乙化与蛋白质稳定性和细胞功能联系起来的分子机制.
主要方法:
- 在人类细胞中进行全基因组的CRISPR淘汰屏幕,以确定遗传相互作用.
- 生物化学分析,以表征由乙转移酶和无素结合酶对蛋白质的识别.
- 在Drosophila中进行功能性测试,以评估N-终端乙化的体内影响.
主要成果:
- 在关键的N-终端乙转移酶 (NatC) 和特定的无素连接酶 (UBR4-KCMF1) 之间发现了显著的遗传依赖.
- NatC和UBR4-KCMF1复合体都能识别含有未乙化N终端甲因的蛋白质,其后是疏水性残留物.
- 松虫中NatC的损失导致男性不育,寿命减少,以及与肌肉缺陷相关的年龄相关的运动能力丧失.
- 一种针对NatC的蛋白质 (UbcE2M) 的过度表达拯救了Drosophila肌肉中的NatC删除表型.
结论:
- 通过NatC介导的N-终端乙化作为对蛋白质降解的保护机制起作用.
- 这种乙化过程对于维持细胞功能,寿命和运动性至关重要.
- N终端乙化和无素结合酶之间的相互作用是真核生物中关键的调节轴.
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