Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA.
Biomolecules. 2023 Sep 29;13(10):1467. doi: 10.3390/biom13101467.
The highly glycosylated S protein plays a vital role in host cell invasion, making it the principal target for vaccine development. Differences in mutations observed on the spike (S) protein of SARS-CoV-2 variants may result in distinct glycosylation patterns, thus influencing immunological evasion, infectivity, and transmissibility. The glycans can mask key epitopes on the S1 protein and alter its structural conformation, allowing the virus to escape the immune system. Therefore, we comprehensively characterize -glycosylation in eleven variants of SARS-CoV-2 S1 subunits to understand the differences observed in the biology of the variants. In-depth characterization was performed with a double digestion strategy and an efficient LC-MS/MS approach. We observed that -glycosylation is highly conserved across all variants in the region between the NTD and RBD, whereas other domains and regions exhibit variation in -glycosylation. Notably, omicron has the highest number of -glycosylation sites on the S1 subunit. Also, omicron has the highest level of sialylation in the RBD and RBM functional motifs. Our findings may shed light on how differences in -glycosylation impact viral pathogenicity in variants of SARS-CoV-2 and facilitate the development of a robust vaccine with high protective efficacy against the variants of concern.
高度糖基化的 S 蛋白在宿主细胞入侵中起着至关重要的作用，使其成为疫苗开发的主要靶点。在 SARS-CoV-2 变体的刺突（S）蛋白上观察到的突变差异可能导致不同的糖基化模式，从而影响免疫逃避、感染性和传染性。聚糖可以掩盖 S1 蛋白上的关键表位并改变其结构构象，使病毒能够逃避免疫系统。因此，我们全面表征了 SARS-CoV-2 S1 亚基的 11 种变体中的 -糖基化，以了解变体生物学中观察到的差异。采用双消化策略和高效 LC-MS/MS 方法进行了深入表征。我们观察到，在 NTD 和 RBD 之间的区域，-糖基化在所有变体中高度保守，而其他结构域和区域的 -糖基化存在差异。值得注意的是，奥密克戎变体在 S1 亚基上具有最多的 -糖基化位点。此外，奥密克戎变体在 RBD 和 RBM 功能基序中具有最高水平的唾液酸化。我们的研究结果可能揭示了 -糖基化差异如何影响 SARS-CoV-2 变体的病毒致病性，并有助于开发针对高关注变体具有高保护效力的强大疫苗。
