脊髓灰质炎病毒3Cpro聚蛋白前体的共同折叠和RNA激活
Grace Campagnola1, Olve Peersen1
1Department of Biochemistry & Molecular Birology, Colorado State University, Fort Collins, Colorado, USA.
The Journal of biological chemistry
|September 17, 2023
概括
脊髓灰质炎病毒的多蛋白加工涉及蛋白酶 (3ABC),其活性由RNA增强. 这种依赖RNA的激活调节了复制中心内的病毒多蛋白质处理.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 阳性链RNA病毒表达由病毒蛋白酶处理的大型多蛋白质.
- 聚蛋白加工产生中间物种,增加病毒基因组多样性和蛋白质功能复杂性.
- 了解蛋白质折叠和聚蛋白前体内的相互作用对于病毒复制至关重要.
研究的目的:
- 研究脊髓灰质炎病毒P3区域蛋白的溶液结构和自我结合 (3A,3B/VPg,3Cpro,3Dpol).
- 描述3ABC多蛋白前体的酶活性和调节.
- 阐明RNA在调节蛋白酶活性和多蛋白质加工中的作用.
主要方法:
- 循环二重化谱法用于分析蛋白质结构.
- 单分子显微镜用于研究蛋白质自我结合.
- 酶活性测定测量蛋白酶功能的测量.
- 对RNA结合的研究,以评估RNA对活性的影响.
主要成果:
- 3A和3B蛋白的共同折叠稳定了3ABC前体内的3C蛋白酶构造.
- 3ABC前体表现出与成熟的3Cpro.pro.相似的蛋白酶活性.
- RNA结合显著刺激3ABCpro的活性,使其比3Cpro具有病毒创造RNA的活性高出20倍.
结论:
- 在3ABC区域内共同折叠产生一种蛋白酶,其活性由RNA局部化调节.
- 通过RNA介导的3ABCpro激活提供了一种控制特定部位病毒聚蛋白加工的机制.
- 这种调节对于病毒复制中心内的病毒复制至关重要.
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