Positive residues of the SARS-CoV-2 fusion domain are key contributors to the initiation of membrane fusion.
| Autor: | Birtles D; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA., Guiyab L; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA., Abbas W; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA., Lee J; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA. Electronic address: jinwoo@umd.edu. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2024 Aug; Vol. 300 (8), pp. 107564. Date of Electronic Publication: 2024 Jul 11. |
| DOI: | 10.1016/j.jbc.2024.107564 |
| Abstrakt: | SARS-CoV-2 is one of the most infectious viruses ever recorded. Despite a plethora of research over the last several years, the viral life cycle is still not well understood, particularly membrane fusion. This process is initiated by the fusion domain (FD), a highly conserved stretch of amino acids consisting of a fusion peptide (FP) and fusion loop (FL), which in synergy perturbs the target cells' lipid membrane to lower the energetic cost necessary for fusion. In this study, through a mutagenesis-based approach, we have investigated the basic residues within the FD (K825, K835, R847, K854) utilizing an in vitro fusion assay and 19 F NMR, validated by traditional 13 C 15 N techniques. Alanine and charge-conserving mutants revealed every basic residue plays a highly specific role within the mechanism of initiating fusion. Intriguingly, K825A led to increased fusogenecity which was found to be correlated to the number of amino acids within helix one, further implicating the role of this specific helix within the FD's fusion mechanism. This work has found basic residues to be important within the FDs fusion mechanism and highlights K825A, a specific mutation made within the FD of the SARS-CoV-2 spike protein, as requiring further investigation due to its potential to contribute to a more virulent strain of SARS-CoV-2. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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