Publication date: Jul 19, 2024
Conformational dynamics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S) mediate exposure of the binding site for the cellular receptor, angiotensin-converting enzyme 2 (ACE2). The N-terminal domain (NTD) of S binds terminal sialic acid (SA) moieties on the cell surface, but the functional role of this interaction in virus entry is unknown. Here, we report that NTD-SA interaction enhances both S-mediated virus attachment and ACE2 binding. Through single-molecule FcF6rster resonance energy transfer imaging of individual S trimers, we demonstrate that SA binding to the NTD allosterically shifts the S conformational equilibrium, favoring enhanced exposure of the ACE2-binding site. Antibodies that target the NTD block SA binding, which contributes to their mechanism of neutralization. These findings inform on mechanisms of S activation at the cell surface.
Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | host |
| disease | VO | Severe acute respiratory syndrome coronavirus 2 |
| disease | VO | Glycoprotein |
| disease | IDO | site |
| drug | DRUGBANK | Angiotensin II |
| disease | VO | report |
| disease | MESH | COVID-19 |