Phosphoregulation of Phase Separation by the SARS-CoV-2 N Protein Suggests a Biophysical Basis for its Dual Functions.
Phosphoregulation of Phase Separation by the SARS-CoV-2 N Protein Suggests a Biophysical Basis for its Dual Functions.
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DOI：
10.1016/j.molcel.2020.11.025
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发表时间：
2020-12-17
期刊：
影响因子：
16
通讯作者：
Morgan DO
中科院分区：
文献类型：
--
作者：
Carlson CR;Asfaha JB;Ghent CM;Howard CJ;Hartooni N;Safari M;Frankel AD;Morgan DO
冠状病毒的核衣壳（N）蛋白具有两个主要功能：病毒体中RNA基因组的压缩和病毒基因转录的调节。目前尚不清楚N蛋白如何介导这些不同的功能。N蛋白包含两个RNA结合结构域，周围是内在紊乱的区域。磷酸化的中心无序区域促进蛋白质的转录功能，但其潜在的机制尚不清楚。在这里，我们表明，N蛋白的SARS冠状病毒-2，与病毒RNA一起，形成生物分子凝聚物。未修饰的N蛋白基于多价RNA-蛋白质和蛋白质-蛋白质相互作用形成部分有序的凝胶样缩合物和离散的15 nm颗粒。磷酸化减少了这些相互作用，产生了更像液体的液滴。我们提出，不同的寡聚状态支持的N蛋白的两个功能：未修饰的蛋白质形成一个结构化的低聚体，适合于核衣壳组装，和磷酸化的蛋白质形成一个液体样的隔间，用于病毒基因组处理。Carlson等人证明SARS-CoV-2的核衣壳（N）蛋白与病毒RNA一起形成凝胶状生物分子凝聚物和颗粒，这与其基因组包装作用一致。磷酸化将缩合物转化为液体样液滴，其可以提供细胞质区室以支持蛋白质在病毒基因组转录中的功能。
The nucleocapsid (N) protein of coronaviruses serves two major functions: compaction of the RNA genome in the virion and regulation of viral gene transcription. It is not clear how the N protein mediates such distinct functions. The N protein contains two RNA-binding domains surrounded by regions of intrinsic disorder. Phosphorylation of the central disordered region promotes the protein’s transcriptional function, but the underlying mechanism is not known. Here, we show that the N protein of SARS-CoV-2, together with viral RNA, forms biomolecular condensates. Unmodified N protein forms partially ordered gel-like condensates and discrete 15-nm particles based on multivalent RNA-protein and protein-protein interactions. Phosphorylation reduces these interactions, generating a more liquid-like droplet. We propose that distinct oligomeric states support the two functions of the N protein: unmodified protein forms a structured oligomer that is suited for nucleocapsid assembly, and phosphorylated protein forms a liquid-like compartment for viral genome processing. Carlson et al. demonstrate that the nucleocapsid (N) protein of SARS-CoV-2, together with viral RNA, forms gel-like biomolecular condensates and particles that are consistent with its genome-packaging role. Phosphorylation transforms condensates into liquid-like droplets, which may provide a cytoplasmic compartment to support the protein’s function in viral genome transcription.
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DOI：
10.1016/j.str.2005.08.021
发表时间：
2005-12
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
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通讯作者：
Lescar J
影响因子：
5.4
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
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作者：
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