PDB files of SARS-CoV-2 Spike Protein Glycoforms

Here we have generated 3D structures of glycoforms of the spike (S) protein SARS-CoV-2, based on reported 3D structures for the S protein and on reported glycomics data for the protein produced in HEK293 cells. We also report structures for glycoforms that represent those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi and ER), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to MD simulation to take into account protein and glycan plasticity, and to determine the extent to which glycan microheterogeneity impacts antigenicity. Lastly, we have identified peptides in the S protein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine.

本研究基于已报道的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突（S）蛋白三维结构，以及在HEK293细胞中表达的该蛋白的糖组学数据，构建了其糖型的三维结构。本研究同时报道了两类糖型的结构：一类对应尚处于高尔基体与内质网酶促修饰阶段之前的新生糖蛋白所携带的糖型，另一类则是其他病毒抗原中常见的糖型。我们对上述模型开展了分子动力学（MD）模拟，以考量蛋白与聚糖的构象可塑性，并明确聚糖微异质性对病毒抗原性的影响程度。最后，本研究鉴定出S蛋白中可能被人类白细胞抗原（HLA）复合物呈递的肽段，并探讨了S蛋白糖基化在调控SARS-CoV-2病毒或相关疫苗适应性免疫应答中的潜在作用。