抑制新型冠状病毒核蛋白的淀粉样蛋白形成。
Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2.
作者信息
Tayeb-Fligelman Einav, Cheng Xinyi, Tai Christen, Bowler Jeannette T, Griner Sarah, Sawaya Michael R, Seidler Paul M, Jiang Yi Xiao, Lu Jiahui, Rosenberg Gregory M, Salwinski Lukasz, Abskharon Romany, Zee Chih-Te, Hou Ke, Li Yan, Boyer David R, Murray Kevin A, Falcon Genesis, Anderson Daniel H, Cascio Duilio, Saelices Lorena, Damoiseaux Robert, Guo Feng, Eisenberg David S
出版信息
bioRxiv. 2021 Mar 18:2021.03.05.434000. doi: 10.1101/2021.03.05.434000.
UNLABELLED
The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid-liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid-liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid-liquid phase separation, suggesting a therapeutic route for Covid-19.
ONE SENTENCE SUMMARY
Atomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics.
未标注
严重急性呼吸综合征冠状病毒2核蛋白（NCAP）在病毒复制和组装过程中参与RNA包装。对其氨基酸序列的计算分析揭示了一个中央低复杂性结构域（LCD），其序列特征类似于已知在液-液相分离中起作用的其他蛋白质中的LCD。在此我们表明，在存在病毒RNA的情况下，NCAP以及单独的其LCD片段在经历液-液相分离时会形成淀粉样纤维。在LCD内，我们鉴定出三个驱动淀粉样纤维形成的6残基片段。我们确定了由这三个鉴定出的片段各自形成的纤维的原子结构。这些结构为我们设计NCAP纤维形成和液-液相分离的肽抑制剂提供了依据，提示了一种治疗新冠肺炎的途径。
一句话总结
来自严重急性呼吸综合征冠状病毒2核蛋白的淀粉样驱动肽段的原子结构为新冠肺炎治疗方法的开发提供了依据。
Zotero 插件