Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
Joel D AllenHimanshi ChawlaFirdaus SamsudinLorena ZuzicAishwary Tukaram ShivganYasunori WatanabeWan-Ting HeSean CallaghanGe SongPeter YongPhilip J M BrouwerYutong SongYongfei CaiHelen M E DuyvesteynTomas MalinauskasJoeri KintPaco PinoMaria J WurmMartin FrankBing ChenDavid I StuartRogier W SandersRaiees AndrabiDennis R BurtonSai LiPeter John BondMax CrispinPublished in: Biochemistry (2021)
A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
Keyphrases
- sars cov
- molecular dynamics simulations
- respiratory syndrome coronavirus
- protein protein
- induced apoptosis
- cell surface
- binding protein
- transcription factor
- genome wide
- cell cycle arrest
- small molecule
- risk assessment
- endothelial cells
- coronavirus disease
- dna methylation
- cell death
- cell free
- climate change
- single molecule
- antibiotic resistance genes