Heterogeneity of Glycan Processing on Trimeric SARS-CoV-2 Spike Protein Revealed by Charge Detection Mass Spectrometry,Journal of the American Chemical Society

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Heterogeneity of Glycan Processing on Trimeric SARS-CoV-2 Spike Protein Revealed by Charge Detection Mass Spectrometry
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-03-03 , DOI: 10.1021/jacs.1c00353
Lohra M Miller ₁ , Lauren F Barnes ₁ , Shannon A Raab ₁ , Benjamin E Draper ₂ , Tarick J El-Baba ₃ , Corinne A Lutomski ₃ , Carol V Robinson ₃ , David E Clemmer ₁ , Martin F Jarrold ₁

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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.

中文翻译：

电荷检测质谱揭示三聚体 SARS-CoV-2 刺突蛋白聚糖加工的异质性

已通过电荷检测质谱 (CDMS) 评估了构成 SARS-CoV-2 病毒刺突 (S) 区域的蛋白质三聚体上 66 个 N-聚糖位点的糖基化相关的异质性。 CDMS 可以同时测量质荷比和单个离子的电荷，从而可以确定高度异质性蛋白质（例如高度糖基化的 S 蛋白三聚体）的质量分布。 CDMS 结果与最近对特定位点聚糖结构和丰度的糖蛋白组学研究进行了比较。有趣的是，通过“自上而下”CDMS 测量确定的平均聚糖质量比“自下而上”糖蛋白质组学研究获得的平均聚糖质量大 35-47%，这表明糖蛋白质组学测量低估了更大、更复杂聚糖的丰度。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宽得多。因此，聚糖质量分布的广度表明 S 蛋白三聚体的聚糖加工程度存在异质性，一些三聚体比其他三聚体加工程度更高。这种异质性可能是作为进一步混淆宿主免疫系统的一种方式而进化的。

更新日期：2021-03-17

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