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像SARS-CoV-2的帕帕因类蛋白酶在细胞内蛋白质的调节中扮演着多个角色

Mei Yang¹, Jennifer Mariano¹, Rebecca Su¹

¹Cancer Innovation Laboratory, Center for Cancer Research, National Institutes of Health, Frederick, Maryland, USA.

The Journal of biological chemistry

|October 14, 2023

概括

SARS-CoV-2 Nsp3 帕帕因样蛋白酶 (PLpro) 通过减少它们的无处不在性来稳定ER相关的降解基质. 这种跨膜蛋白还会分裂ER居住蛋白,影响脂质生物合成调节器.

科学领域:

病毒学病毒学
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

冠状病毒利用含有帕帕因类蛋白酶 (PLpro) 的大型非结构性蛋白质 (Nsp3) 进行聚蛋白加工.
SARS-CoV PLpro 呈现出双化和脱化活性,并且局部存在于内质网膜 (ER).

研究的目的:

为了调查SARS-CoV-2 Nsp3 PLpro的二氧化活性是否影响ER相关降解 (ERAD) 基质.
为了确定SARS-CoV-2 Nsp3 PLpro对涉及脂质生物合成的特定ERAD基质的影响.

主要方法:

全长和截断的跨膜SARS-CoV-2 Nsp3与三个ERAD基质 (INSIG-1,SREBP-1,SREBP-2) 的同时表达.
分析蛋白质含量,无处不在状态和裂变部位.
位点定向突变发生,以调查特定裂变点和降解点的作用.

主要成果:

跨膜SARS-CoV-2 Nsp3 PLpro增加了INSIG-1水平并降低了其无处不在.
跨膜PLpro在多个部位分裂了SREBP-1,减少了它的前体.
跨膜PLpro在正规部位分离了SREBP-2,增加了其水平,即使在降解基因发生突变时也稳定了SREBP-2,与减少的无处不在相关.

结论:

定于ER的SARS-CoV-2 Nsp3 PLpro作为一个二化酶,稳定了ERAD基质.
SARS-CoV-2 Nsp3 PLpro可以在规范和非规范位置分裂ER居民蛋白质,可能会影响超出已建立的共识序列的蛋白质稳定性和功能.

关键词:

在这里,我们可以看到COVID COVID COVID.在ISG15中,我们可以看到ISG15.在 Nsp Nsp 的情况下.细胞生物学细胞生物学胆固醇胆固醇胆固醇是一种没有二维基因酸酶.没有除化酶的酶.必须进行脱离分离.这是先天免疫力.干扰子干扰子干扰子脂质生物合成脂质生物合成蛋白质溶解过程中的蛋白质溶解.在任何地方都是无处不在的.病毒学病毒学毒性因子是毒性因子.

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