Yamamoto, Y.; Inoue, T.; Inoue, M.; Murae, M.; Fukasawa, M.; Kaneko, M.K.; Kato, Y.; Noguchi, K. SARS-CoV-2 Spike Protein Mutation at Cysteine-488 Impairs Its Golgi Localization and Intracellular S1/S2 Processing. Int. J. Mol. Sci.2022, 23, 15834.
Yamamoto, Y.; Inoue, T.; Inoue, M.; Murae, M.; Fukasawa, M.; Kaneko, M.K.; Kato, Y.; Noguchi, K. SARS-CoV-2 Spike Protein Mutation at Cysteine-488 Impairs Its Golgi Localization and Intracellular S1/S2 Processing. Int. J. Mol. Sci. 2022, 23, 15834.
Yamamoto, Y.; Inoue, T.; Inoue, M.; Murae, M.; Fukasawa, M.; Kaneko, M.K.; Kato, Y.; Noguchi, K. SARS-CoV-2 Spike Protein Mutation at Cysteine-488 Impairs Its Golgi Localization and Intracellular S1/S2 Processing. Int. J. Mol. Sci.2022, 23, 15834.
Yamamoto, Y.; Inoue, T.; Inoue, M.; Murae, M.; Fukasawa, M.; Kaneko, M.K.; Kato, Y.; Noguchi, K. SARS-CoV-2 Spike Protein Mutation at Cysteine-488 Impairs Its Golgi Localization and Intracellular S1/S2 Processing. Int. J. Mol. Sci. 2022, 23, 15834.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cell receptor angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert its fusiogenic activity, the spike protein is typically processed at a specific site (S1/S2 site) by cellular proteases such as furin. The C488 residue, located at the spike–ACE2 interacting surface, is critical for the fusiogenic and infectious roles of the SARS-CoV-2 spike protein. We further demonstrated that the C488 residue of spike protein is involved in subcellular targeting and S1/S2 processing. C488 mutant spike localization to the Golgi apparatus and cell surface were impaired. Consequently, the S1/S2 processing of the spike protein, probed by anti-Ser-686-cleaved spike antibody, markedly decreased in C488 mutant spike proteins. Moreover, brefeldin A-mediated endoplasmic reticulum-to-Golgi traffic suppression also suppressed spike protein S1/S2 processing. As brefeldin A treatment and C488 mutation inhibited S1/S2 processing and syncytia formation, the C488 residue of spike protein is required for functional spike protein processing.
Keywords
SARS-CoV-2; Spike; Cysteine; proteolysis; brefeldin A
Subject
Biology and Life Sciences, Virology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
