Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid.
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 Foerster 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.
Mesh Terms:
Allosteric Regulation, Angiotensin-Converting Enzyme 2, Binding Sites, COVID-19, Fluorescence Resonance Energy Transfer, Humans, N-Acetylneuraminic Acid, Protein Binding, Protein Domains, SARS-CoV-2, Single Molecule Imaging, Spike Glycoprotein, Coronavirus, Virus Attachment, Virus Internalization
Allosteric Regulation, Angiotensin-Converting Enzyme 2, Binding Sites, COVID-19, Fluorescence Resonance Energy Transfer, Humans, N-Acetylneuraminic Acid, Protein Binding, Protein Domains, SARS-CoV-2, Single Molecule Imaging, Spike Glycoprotein, Coronavirus, Virus Attachment, Virus Internalization
Sci Adv
Date: Jul. 19, 2024
PubMed ID: 39018397
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