Comprehensive O-Glycosylation Analysis of the SARS-CoV-2 Spike Protein with Biomimetic Trp-Arg Materials
Comprehensive O-Glycosylation Analysis of the SARS-CoV-2 Spike Protein with Biomimetic Trp-Arg Materials
复制标题
使用仿生色氨酸-精氨酸材料对 SARS-CoV-2 刺突蛋白进行全面的 O-糖基化分析。
DOI：
10.1021/acs.analchem.0c04634
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发表时间：
2021-07-20
影响因子：
7.4
通讯作者：
Liang, Xinmiao
中科院分区：
文献类型：
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作者：
Dong, Xuefang;Chen, Cheng;Liang, Xinmiao
由严重急性呼吸综合征冠状病毒-2 （SARS-CoV-2）引起的COVID-19大流行是严重的公共卫生威胁。大多数针对SARS-CoV-2的疫苗靶向高度糖基化的刺突蛋白(S)。充分了解这种蛋白的糖基化谱是成功研制疫苗的关键。与sars - cov - 2s上已确认的22个n -糖基化位点不同，该蛋白上仅报道了几个o -糖基化位点。这种差异主要是由于o -糖基化的化学计量量极低。在此，我们设计了仿生材料Trp-Arg （WR）单体接枝二氧化硅微球（简称WR- sio2），这些仿生材料可以高选择性地富集N-和o -连接的糖肽。WR-SiO2在o链糖肽富集过程中可以抵抗非糖肽对BSA 100摩尔折叠的干扰。我们利用WR-SiO2对重组SARS-CoV-2 s的o糖基化谱进行了全面分析，在SARS-CoV-2 s上鉴定出27个o糖基化位点，其中包括18个明确位点。我们的研究表明，这种仿生聚合物对o链糖肽具有特异性选择性，为生物领域的o糖基化研究铺平了道路。sars - cov - 2s的o -糖基化谱可能是对sars - cov - 2s除n -糖基化外的全面糖基化的补充。
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious public health threat. Most vaccines against SARS-CoV-2 target the highly glycosylated spike protein (S). A good knowledge of the glycosylation profile of this protein is key to successful vaccine development. Unlike the 22 confirmed N-glycosylation sites on SARS-CoV-2 S, only a few O-glycosylation sites on this protein have been reported. This difference is mainly ascribed to the extremely low stoichiometry of O-glycosylation. Herein, we designed the biomimetic materials, Trp-Arg (WR) monomer-grafted silica microspheres (designated as WR-SiO2), and these biomimetic materials can enrich N- and O-linked glycopeptides with high selectivity. And WR-SiO2 can resist the nonglycopeptides' interference with the 100 molar fold of BSA during O-linked glycopeptide enrichment. We utilized WR-SiO2 to comprehensively analyze the O-glycosylation profile of recombinant SARS-CoV-2 S. Twenty-seven O-glycosylation sites including 18 unambiguous sites are identified on SARS-CoV-2 S. Our study demonstrates that the biomimetic polymer can offer specific selectivity for O-linked glycopeptides and pave the way for O-glycosylation research in biological fields. The O-glycosylation profile of SARS-CoV-2 S might supplement the comprehensive glycosylation in addition to N-glycosylation of SARS-CoV-2 S.