PARP14是一种具有ADP-ribosyl转移酶和酶活动的PARP
Nina Đukić1, Øyvind Strømland1,2, Jonas Damgaard Elsborg3
1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Science advances
|September 13, 2023
概括
聚 (ADP-ribose) 聚合酶14 (PARP14) 是一种具有酶活性的双功能酶. 它的宏域1逆转PARP14 ADP-ribosylation,影响细胞过程和抗病毒反应.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 多 (ADP-ribose) 聚合酶14 (PARP14) 调节免疫力,转录和DNA复制压力.
- PARP14的酶活性和基质,特别是其ADP-ribosylation逆转机制,仍然在很大程度上没有特征.
研究的目的:
- 阐明PARP14的酶功能,重点关注其ADP-ribosyl转移酶和酶活性.
- 为了确定PARP14介导的ADP-ribosylation的基质和调节机制.
- 为了研究PARP14的宏1在它的酶活性和细胞功能中的作用.
主要方法:
- 生物化学试验评估PARP14及其突变体的ADP-ribosyl转移酶和酶活性.
- 细胞表达PARP14突变,以分析体内ADP-ribosylation水平和细胞表型.
- 在体外和细胞测试以评估SARS-CoV-2 Nsp3 Mac1域在PARP14上的相互作用和活性.
主要成果:
- PARP14表现出双重酶功能,在蛋白质和核酸基质上充当ADP-ribosyl转移酶和酶.
- 帕尔P14的1大域具有活跃的ADP-ribosyl酸酶活性,帕尔P9的1大域也是如此.
- 在PARP14中对宏基因1的失活会导致人体细胞中蛋白质单基化增加,影响PARP14,PARP13,并诱导特定的细胞表型.
- 在SARS-CoV-2 Nsp3 Mac1域有效地逆转PARP14ADP-ribosylation在体外和细胞内.
结论:
- PARP14是一种对调节细胞ADP-ribosylation至关重要的双功能酶.
- PARP14的宏域1的酶活性在逆转其自身的ADP-ribosylation中起着关键作用.
- 像SARS-CoV-2 Nsp3 Mac1这样的病毒宏观域可以抵消宿主PARP14介导的抗病毒反应,这表明一种进化适应.
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