Site-specific steric control of SARS-CoV-2 spike glycosylation
Site-specific steric control of SARS-CoV-2 spike glycosylation
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DOI：
10.1101/2021.03.08.433764
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发表时间：
2021-03
期刊：
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通讯作者：
Joel D. Allen;H. Chawla;Firdaus Samsudin;Lorena Zuzic;A. T. Shivgan;Yasunori Watanabe;Wan-ting He;Sean Callaghan;G. Song;Peter Yong;P. Brouwer;Yutong Song;Yongfei Cai;Helen M. E. Duyvesteyn;T. Malinauskas;J. Kint;P. Pino;Maria J. Wurm;M. Frank;Bing Chen;D. Stuart;R. Sanders;R. Andrabi;D. Burton;Sai Li;P. Bond;M. Crispin
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作者：
Joel D. Allen;H. Chawla;Firdaus Samsudin;Lorena Zuzic;A. T. Shivgan;Yasunori Watanabe;Wan-ting He;Sean Callaghan;G. Song;Peter Yong;P. Brouwer;Yutong Song;Yongfei Cai;Helen M. E. Duyvesteyn;T. Malinauskas;J. Kint;P. Pino;Maria J. Wurm;M. Frank;Bing Chen;D. Stuart;R. Sanders;R. Andrabi;D. Burton;Sai Li;P. Bond;M. Crispin
疫苗设计的一个中心原则是在引发保护性免疫时展示天然样抗原。 SARS-CoV-2 刺突蛋白中大量的 N 连接聚糖是正在研究的许多不同候选疫苗之间异质性的潜在来源。在这里，我们研究了来自五个不同实验室的重组 SARS-CoV-2 刺突蛋白的糖基化，并将它们与传染性病毒 S 蛋白进行比较。我们发现所有样品中都保守的模式，这可能与聚糖成熟的位点特异性停滞相关，聚糖成熟的停滞充当蛋白质结构的高度敏感的报告者。完全糖基化尖峰的分子动力学 (MD) 模拟支持塑造聚糖酶促加工的空间限制模型。这些结果表明，基于重组刺突的 SARS-CoV-2 免疫原糖基化可重复地重现病毒糖基化的特征。
A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity between the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against infectious virus S protein. We find patterns which are conserved across all samples and this can be associated with site-specific stalling of glycan maturation which act as a highly sensitive reporter of protein structure. Molecular dynamics (MD) simulations of a fully glycosylated spike support s a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.