Sun Zeyu, Zheng Xiaoqin, Ji Feiyang, Zhou Menghao, Su Xiaoling, Ren Keyi, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Infect Microbes Dis. 2021 Aug 3;3(3):149-157. doi: 10.1097/IM9.0000000000000071. eCollection 2021 Sep.
The devastating coronavirus disease 2019 (COVID-19) pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its viral components. Compared to the Spike protein, which is the primary target for currently available vaccines or antibodies, knowledge about other virion structural components is incomplete. Using high-resolution mass spectrometry, we report a comprehensive post-translational modification (PTM) analysis of nucleocapsid phosphoprotein (NCP), the most abundant structural component of the SARS-CoV-2 virion. In addition to phosphoryl groups, we show that the SARS-CoV-2 NCP is decorated with a variety of PTMs, including -glycans and ubiquitin. Based on newly identified PTMs, refined protein structural models of SARS-CoV-2 NCP were proposed and potential immune recognition epitopes of NCP were aligned with PTMs. These data can facilitate the design of novel vaccines or therapeutics targeting NCP, as valuable alternatives to the current vaccination and treatment paradigm that is under threat of the ever-mutating SARS-CoV-2 Spike protein.
2019年冠状病毒病（COVID-19）大流行促使全球致力于研究严重急性呼吸综合征冠状病毒2（SARS-CoV-2）及其病毒成分的结构生物学特性。与作为当前可用疫苗或抗体主要靶点的刺突蛋白相比，关于病毒体其他结构成分的了解尚不完整。我们使用高分辨率质谱法，报告了对核衣壳磷蛋白（NCP）的全面翻译后修饰（PTM）分析，NCP是SARS-CoV-2病毒体中最丰富的结构成分。除了磷酸基团外，我们还表明SARS-CoV-2 NCP带有多种PTM，包括聚糖和泛素。基于新鉴定的PTM，提出了SARS-CoV-2 NCP的精细蛋白质结构模型，并将NCP潜在的免疫识别表位与PTM进行了比对。这些数据有助于设计针对NCP的新型疫苗或疗法，作为当前疫苗接种和治疗模式的有价值替代方案，而当前模式正受到不断变异的SARS-CoV-2刺突蛋白的威胁。
