Palmitoylation of SARS-CoV-2 S protein is critical for S-mediated syncytia formation and virus entry.

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  • Additional Information
    • Source:
      Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7705876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-9071 (Electronic) Linking ISSN: 01466615 NLM ISO Abbreviation: J Med Virol Subsets: MEDLINE
    • Publication Information:
      Publication: New York Ny : Wiley-Liss
      Original Publication: New York, Liss.
    • Subject Terms:
      Virus Internalization*; Cell Membrane/*metabolism ; Giant Cells/*metabolism ; Lipoylation/*physiology ; Spike Glycoprotein, Coronavirus/*metabolism; 4-Butyrolactone/analogs & derivatives ; 4-Butyrolactone/pharmacology ; Acyltransferases/antagonists & inhibitors ; COVID-19/pathology ; Cell Line ; HEK293 Cells ; Humans ; Protein Processing, Post-Translational/physiology
    • Abstract:
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The S protein is the key viral protein for associating with ACE2, the receptor for SARS-CoV-2. There are many kinds of posttranslational modifications in S protein. However, the detailed mechanism of palmitoylation of SARS-CoV-2 S remains to be elucidated. In our current study, we characterized the palmitoylation of SARS-CoV-2 S. Both the C15 and cytoplasmic tail of SARS-CoV-2 S were palmitoylated. Fatty acid synthase inhibitor C75 and zinc finger DHHC domain-containing palmitoyltransferase (ZDHHC) inhibitor 2-BP reduced the palmitoylation of S. Interestingly, palmitoylation of SARS-CoV-2 S was not required for plasma membrane targeting of S but was critical for S-mediated syncytia formation and SARS-CoV-2 pseudovirus particle entry. Overexpression of ZDHHC2, ZDHHC3, ZDHHC4, ZDHHC5, ZDHHC8, ZDHHC9, ZDHHC11, ZDHHC14, ZDHHC16, ZDHHC19, and ZDHHC20 promoted the palmitoylation of S. Furthermore, those ZDHHCs were identified to associate with SARS-CoV-2 S. Our study not only reveals the mechanism of S palmitoylation but also will shed important light into the role of S palmitoylation in syncytia formation and virus entry.
      (© 2021 Wiley Periodicals LLC.)
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    • Contributed Indexing:
      Keywords: SARS-CoV-2; ZDHHC; palmitoylation; spike; syncytia
    • Accession Number:
      0 (4-methylene-2-octyl-5-oxofuran-3-carboxylic acid)
      0 (Spike Glycoprotein, Coronavirus)
      0 (spike protein, SARS-CoV-2)
      EC 2.3.- (Acyltransferases)
      EC 2.3.1.- (ZDHHC1 protein, human)
      OL659KIY4X (4-Butyrolactone)
    • Publication Date:
      Date Created: 20210916 Date Completed: 20211123 Latest Revision: 20211211
    • Publication Date:
      20250114
    • Accession Number:
      PMC8661603
    • Accession Number:
      10.1002/jmv.27339
    • Accession Number:
      34528721