Spike protein gets palmitoylated

Stable Identifier
R-HSA-9694341
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
endoplasmic reticulum-Golgi intermediate compartment
ReviewStatus
5/5
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Spike protein gets palmitoylated
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Palmitoylation of SARS-CoV-2 Spike can occur on multiple different cysteine residues in the S2 endodomain; however, palmitoylation appears to occur more efficiently on the N-terminal endodomain cysteines. Inhibition of palmitoylation reduced the proteolytic processing of the full (S1+S2 precursor) Spike protein (Nguyen et al, 2020). Treatment with a protein palmitoylation inhibitor suppresses S-mediated membrane fusion and the entry of SARS-CoV-2 pseudovirus into host cells. In a Spike mutant lacking Cys residues at the C-terminus the palmitoylation was completely abolished, with a decrease of S-trimer formation. The host proteins ZDHHC5 and GOLGA7 were found to enhance SARS-CoV-2 S protein palmitoylation synergistically, so the involvement of the ZDHHC5:GOLGA7 palmitoyltransferase complex in SARS-CoV-2 Spike palmitoylation seems likely (Wu ZC et al, 2021; Zeng et al, 2021; Nguyen et al, 2020; Lee et al, 2020). Further investigations showed the possible participation of other host palmitoylation complexes acting on different sites in the Spike protein (Mesquita et al, 2021; Puthenveetil et al, 2021; Li DQ et al, 2022). We included palmitoyltransferases in the annotation that had the support of at least two papers.
Literature References
PubMed ID Title Journal Year
34528721 Palmitoylation of SARS-CoV-2 S protein is critical for S-mediated syncytia formation and virus entry

Li, D, Liu, Y, Lu, Y, Gao, S, Zhang, L

J Med Virol 2022
33310888 Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects

Nguyen, HT, Zhang, S, Wang, Q, Anang, S, Wang, J, Ding, H, Kappes, JC, Sodroski, J

J Virol 2020
34599882 S-acylation controls SARS-CoV-2 membrane lipid organization and enhances infectivity

Mesquita, FS, Abrami, L, Sergeeva, O, Turelli, P, Qing, E, Kunz, B, Raclot, C, Paz Montoya, J, Abriata, LA, Gallagher, T, Dal Peraro, M, Trono, D, D'Angelo, G, van der Goot, FG

Dev Cell 2021
34428449 S-acylation of SARS-CoV-2 spike protein: Mechanistic dissection, in vitro reconstitution and role in viral infectivity

Puthenveetil, R, Lun, CM, Murphy, RE, Healy, LB, Vilmen, G, Christenson, ET, Freed, EO, Banerjee, A

J Biol Chem 2021
34961524 The interactions of ZDHHC5/GOLGA7 with SARS-CoV-2 spike (S) protein and their effects on S protein's subcellular localization, palmitoylation and pseudovirus entry

Zeng, XT, Yu, XX, Cheng, W

Virol J 2021
  Fatty Acid Synthase inhibition prevents palmitoylation of SARS-CoV2 Spike Protein and improves survival of mice infected with murine hepatitis virus

Lee, M, Sugiyama, M, Mekhail, K, Khosraviani, N, Wei, K, Lee, WL, Antonescu, C, Fairn, GD

   
34117209 Palmitoylation of SARS-CoV-2 S protein is essential for viral infectivity

Wu, Z, Zhang, Z, Wang, X, Zhang, J, Ren, C, Li, Y, Gao, L, Liang, X, Wang, P, Ma, C

Signal Transduct Target Ther 2021
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein-cysteine S-palmitoyltransferase activity of Palmitoyltransferases [Golgi membrane]

Physical Entity
Palmitoyltransferases [Golgi membrane] (Homo sapiens)
Activity
protein-cysteine S-palmitoyltransferase activity (GO:0019706)
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Cross References
Mondo
Authored
Stephan, R  (2020-07-22)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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