Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
01 May 2020
01 May 2020
Historique:
entrez:
9
6
2020
pubmed:
9
6
2020
medline:
9
6
2020
Statut:
epublish
Résumé
Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein 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. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight (17% for the HEK293 glycoform) the level of surface shielding is disproportionately high at 42%.
Identifiants
pubmed: 32511307
doi: 10.1101/2020.04.07.030445
pmc: PMC7217288
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103390
Pays : United States
Commentaires et corrections
Type : UpdateIn
Déclaration de conflit d'intérêts
Competing Interests The authors declare no competing interests.
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