宿主血清蛋白酶ACOT2通过水解病毒多蛋白质来帮助DENV增殖
Sen Ma1, Sai Shi1, Binghong Xu1
1Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, School of Life Sciences, Tianjin University, Tianjin, China.
mSystems
|December 19, 2023
概括
研究人员发现,acyl-CoA thioesterase 2 (ACOT2) 作为一种血清蛋白酶,分裂病毒多蛋白,以帮助登革热病毒 (DENV) 复制. 这一发现为DENV感染和潜在的抗病毒策略提供了新的见解.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 登革热病毒 (DENV) 导致登革热,这是一个重要的全球健康问题.
- DENV复制依赖于病毒和宿主蛋白酶的多蛋白质处理.
- 主体蛋白酶在DENV增殖中的确切作用尚未完全理解.
研究的目的:
- 用基于酸的探针 (FP) 研究宿主血清蛋白酶在DENV感染中的作用.
- 为了识别和描述与DENV复制机器相互作用的宿主蛋白酶.
- 阐明宿主蛋白酶对DENV传播有所贡献的机制.
主要方法:
- 在DENV感染期间利用基于酸的探针 (FPs) 识别高调主体血清蛋白酶.
- 进行了酶定量测试,以确认在DENV多基板上的已识别的蛋白酶的裂变活性.
- 进行病毒学实验,以评估蛋白酶活性对DENV传播的影响.
- 采用对接模型来可视化蛋白酶-基质相互作用和催化机制.
主要成果:
- 鉴定了乙基-CoA硫酶2 (ACOT2) 作为宿主血清蛋白酶,表现出对DENV多蛋白的分裂活性.
- 证实ACOT2在病毒复制阶段直接促进DENV的传播.
- 首次证明,ACOT2作为一种能够化蛋白质基质的血清蛋白酶.
- 提供了ACOT2对病毒多的结合和催化活性的分子洞察力.
结论:
- 通过处理病毒多蛋白质,ACOT2在促进DENV复制方面发挥着至关重要的作用.
- 这项研究确立了ACOT2作为参与DENV生命周期的血清蛋白酶.
- 这些发现为开发针对登革热的抗病毒策略提供了新的目标.
- 基于活动的蛋白质组学可以有效地揭示复杂的宿主病毒相互作用.
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