Heterogeneity of Glycan Processing on Trimeric SARS-CoV-2 Spike Protein Revealed by Charge Detection Mass Spectrometry.
Heterogeneity of Glycan Processing on Trimeric SARS-CoV-2 Spike Protein Revealed by Charge Detection Mass Spectrometry.
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DOI：
10.1021/jacs.1c00353
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发表时间：
2021-03-17
影响因子：
15
通讯作者：
Jarrold MF
中科院分区：
文献类型：
--
作者：
Miller LM;Barnes LF;Raab SA;Draper BE;El-Baba TJ;Lutomski CA;Robinson CV;Clemmer DE;Jarrold MF
利用电荷检测质谱法（CDMS）评估了构成SARS-CoV-2病毒刺突(S)区的蛋白三聚体上66个n -聚糖位点糖基化的异质性。CDMS允许同时测量单个离子的质量电荷比和电荷，因此可以确定高度异质蛋白的质量分布，例如重度糖基化的S蛋白三聚体。CDMS结果与最近糖蛋白组学研究的结构和特定位点的聚糖丰度进行了比较。有趣的是，通过“自上而下”的CDMS测量确定的平均聚糖质量比“自下而上”的糖蛋白组学研究获得的糖蛋白质量大35-47%，这表明糖蛋白组学测量低估了更大、更复杂的聚糖的丰度。此外，假设每个三聚体上的聚糖加工不相关，CDMS确定的聚糖质量分布比糖蛋白组学研究预期的分布要广泛得多。因此，聚糖质量分布的宽度表明S蛋白三聚体的聚糖加工程度的异质性，一些三聚体比其他三聚体加工得更重。这种异质性可能已经进化为进一步混淆宿主免疫系统的一种方式。
The heterogeneity associated with glycosylation of the 66 N-glycan sites on the protein trimer making up the spike (S) region of the SARS-CoV-2 virus has been assessed by charge detection mass spectrometry (CDMS). CDMS allows simultaneous measurement of the mass-to-charge ratio and charge of individual ions, so that mass distributions can be determined for highly heterogeneous proteins such as the heavily glycosylated S protein trimer. The CDMS results are compared to recent glycoproteomics studies of the structure and abundance of glycans at specific sites. Interestingly, average glycan masses determined by “top-down” CDMS measurements are 35–47% larger than those obtained from the “bottom-up” glycoproteomics studies, suggesting that the glycoproteomic measurements underestimated the abundances of larger, more-complex glycans. Moreover, the distribution of glycan masses determined by CDMS is much broader than the distribution expected from the glycoproteomics studies, assuming that glycan processing on each trimer is not correlated. The breadth of the glycan mass distribution therefore indicates heterogeneity in the extent of glycan processing of the S protein trimers, with some trimers being much more heavily processed than others. This heterogeneity may have evolved as a way of further confounding the host’s immune system.
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DOI：
10.1007/s13361-018-2038-3
发表时间：
2018-11-01
影响因子：
3.2
作者：
Draper, Benjamin E.;Anthony, Staci N.;Jarrold, Martin F.
通讯作者：
Jarrold, Martin F.
影响因子：
56.9
作者：
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通讯作者：
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影响因子：
3.7
作者：
Stertz S;Reichelt M;Spiegel M;Kuri T;Martínez-Sobrido L;García-Sastre A;Weber F;Kochs G
通讯作者：
Kochs G
影响因子：
24.1
作者：
Tai, Wanbo;He, Lei;Du, Lanying
通讯作者：
Du, Lanying
影响因子：
4.3
作者：
Shajahan, Asif;Supekar, Nitin T.;Azadi, Parastoo
通讯作者：
Azadi, Parastoo