Contributions of the N-terminal intrinsically disordered region of the severe acute respiratory syndrome coronavirus 2 nucleocapsid protein to RNA-induced phase separation.
Contributions of the N-terminal intrinsically disordered region of the severe acute respiratory syndrome coronavirus 2 nucleocapsid protein to RNA-induced phase separation.
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DOI：
10.1002/pro.4409
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发表时间：
2022-09
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影响因子：
--
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严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）核衣壳蛋白是成熟病毒粒子的重要结构成分，包裹基因组RNA并调节RNA的转录和复制。它的几种活性可能与蛋白质进行液-液相分离的能力有关。NSARS-CoV-2在其N末端（NTE）含有一个固有的无序区域，该区域可以被磷酸化，并受到人类COVID-19感染中发现的突变的影响，包括在Omicron变异中。在这里，我们表明NTE缺失降低了可以诱导NSARS-CoV-2相分离的RNA浓度范围。此外，朊病毒样NTE的缺失允许NSARS-CoV-2液滴在孵育期间保持其液体样性质。我们进一步证明，RNA结合参与NTE的多个部分，并改变NTE的结构特性。这些结果构成了表征N末端突变和翻译后修饰对SARS-CoV-2核衣壳蛋白分子特性影响的基础。SARS-CoV-2的核衣壳蛋白在宿主感染后的基因组包装和病毒复制中起着重要作用。复制与RNA诱导的核衣壳蛋白的液-液相分离有关。我们提出的见解的N-末端部分的核衣壳蛋白在蛋白质的RNA介导的液-液相分离的作用。
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleocapsid protein is an essential structural component of mature virions, encapsulating the genomic RNA and modulating RNA transcription and replication. Several of its activities might be associated with the protein's ability to undergo liquid–liquid phase separation. NSARS‐CoV‐2 contains an intrinsically disordered region at its N‐terminus (NTE) that can be phosphorylated and is affected by mutations found in human COVID‐19 infections, including in the Omicron variant of concern. Here, we show that NTE deletion decreases the range of RNA concentrations that can induce phase separation of NSARS‐CoV‐2. In addition, deletion of the prion‐like NTE allows NSARS‐CoV‐2 droplets to retain their liquid‐like nature during incubation. We further demonstrate that RNA‐binding engages multiple parts of the NTE and changes NTE's structural properties. The results form the foundation to characterize the impact of N‐terminal mutations and post‐translational modifications on the molecular properties of the SARS‐CoV‐2 nucleocapsid protein. The nucleocapsid protein of SARS‐CoV‐2 plays an important role in both genome packaging and viral replication upon host infection. Replication has been associated with RNA‐induced liquid–liquid phase separation of the nucleocapsid protein. We present insights into the role of the N‐terminal part of the nucleocapsid protein in the protein's RNA‐mediated liquid–liquid phase separation.
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