Glycans on the SARS-CoV-2 Spike Control the Receptor Binding Domain Conformation.
bioRxiv
; 2020 Jun 30.
Article
em En
| MEDLINE
| ID: mdl-32637959
ABSTRACT
The glycan shield of the beta-coronavirus (ß-CoV) Spike (S) glycoprotein provides protection from host immune responses, acting as a steric block to potentially neutralizing antibody responses. The conformationally dynamic S-protein is the primary immunogenic target of vaccine design owing to its role in host-cell fusion, displaying multiple receptor binding domain (RBD) 'up' and 'down' state configurations. Here, we investigated the potential for RBD adjacent, N-terminal domain (NTD) glycans to influence the conformational equilibrium of these RBD states. Using a combination of antigenic screens and high-resolution cryo-EM structure determination, we show that an N-glycan deletion at position 234 results in a dramatically reduced population of the 'up' state RBD position. Conversely, glycan deletion at position N165 results in a discernable increase in 'up' state RBDs. This indicates the glycan shield acts not only as a passive hinderance to antibody meditated immunity but also as a conformational control element. Together, our results demonstrate this highly dynamic conformational machine is responsive to glycan modification with implications in viral escape and vaccine design.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Revista:
BioRxiv
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos