Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39747000.
- Also identified by DOI 10.1038/s41467-024-55358-9 and PMC identifier 11696146.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The SARS-CoV-2 spike protein's membrane-binding domain bridges the viral and host cell membrane, a critical step in triggering membrane fusion. Here, we investigate how the SARS-CoV-2 spike protein interacts with host cell membranes, focusing on a membrane-binding peptide (MBP) located near the TMPRSS2 cleavage site. Through in vitro and computational studies, we examine both primed (TMPRSS2-cleaved) and unprimed versions of the MBP, as well as the influence of its conserved disulfide bridge on membrane binding. Our results show that the MBP preferentially associates with cholesterol-rich membranes, and we find that cholesterol depletion significantly reduces viral infectivity. Furthermore, we observe that the disulfide bridge stabilizes the MBP's interaction with the membrane, suggesting a structural role in viral entry. Together, these findings highlight the importance of membrane composition and peptide structure in SARS-CoV-2 infectivity and suggest that targeting the disulfide bridge could provide a therapeutic strategy against infection.
Medical subject headings
- Spike Glycoprotein, Coronavirus
- SARS-CoV-2
- Cell Membrane
- Microscopy, Atomic Force
- Protein Binding
- Cholesterol