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Glycosylation and S-palmitoylation regulate SARS-CoV-2 spike protein intracellular trafficking
oleh: Chih-Feng Tien, Wan-Ting Tsai, Chun Hwa Chen, Hui-Ju Chou, Mingzi M. Zhang, Jhe-Jhih Lin, En-Ju Lin, Shih-Syong Dai, Yueh-Hsin Ping, Chia-Yi Yu, Yi-Ping Kuo, Wei-Hsiang Tsai, Hsin-Wei Chen, Guann-Yi Yu
Format: | Article |
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Diterbitkan: | Elsevier 2022-08-01 |
Deskripsi
Summary: Post-translational modifications (PTMs), such as glycosylation and palmitoylation, are critical to protein folding, stability, intracellular trafficking, and function. Understanding regulation of PTMs of SARS-CoV-2 spike (S) protein could help the therapeutic drug design. Herein, the VSV vector was used to produce SARS-CoV-2 S pseudoviruses to examine the roles of the 611LYQD614 and cysteine-rich motifs in S protein maturation and virus infectivity. Our results show that 611LY612 mutation alters S protein intracellular trafficking and reduces cell surface expression level. It also changes S protein glycosylation pattern and decreases pseudovirus infectivity. The S protein contains four cysteine-rich clusters with clusters I and II as the main palmitoylation sites. Mutations of clusters I and II disrupt S protein trafficking from ER-to-Golgi, suppress pseudovirus production, and reduce spike-mediated membrane fusion activity. Taken together, glycosylation and palmitoylation orchestrate the S protein maturation processing and are critical for S protein-mediated membrane fusion and infection.