Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55358-9 |
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| author | Qingrong Zhang Raissa S. L. Rosa Ankita Ray Kimberley Durlet Gol Mohammad Dorrazehi Rafael C. Bernardi David Alsteens |
| author_facet | Qingrong Zhang Raissa S. L. Rosa Ankita Ray Kimberley Durlet Gol Mohammad Dorrazehi Rafael C. Bernardi David Alsteens |
| author_sort | Qingrong Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5a0e01ae4c6d480b9d44cffbd707454c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5a0e01ae4c6d480b9d44cffbd707454c2025-01-05T12:37:40ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-024-55358-9Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopyQingrong Zhang0Raissa S. L. Rosa1Ankita Ray2Kimberley Durlet3Gol Mohammad Dorrazehi4Rafael C. Bernardi5David Alsteens6Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Croix du sud 4-5, L7.07.07Department of Chemistry and Biochemistry, Auburn UniversityLouvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Croix du sud 4-5, L7.07.07Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Croix du sud 4-5, L7.07.07Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Croix du sud 4-5, L7.07.07Department of Chemistry and Biochemistry, Auburn UniversityLouvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, Croix du sud 4-5, L7.07.07Abstract 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.https://doi.org/10.1038/s41467-024-55358-9 |
| spellingShingle | Qingrong Zhang Raissa S. L. Rosa Ankita Ray Kimberley Durlet Gol Mohammad Dorrazehi Rafael C. Bernardi David Alsteens Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy Nature Communications |
| title | Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy |
| title_full | Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy |
| title_fullStr | Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy |
| title_full_unstemmed | Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy |
| title_short | Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy |
| title_sort | probing sars cov 2 membrane binding peptide via single molecule afm based force spectroscopy |
| url | https://doi.org/10.1038/s41467-024-55358-9 |
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