Rafting through the palms: S-acylation of SARS-CoV-2 spike protein induces lipid reorganization
| Autor: | Anirban Banerjee, Geraldine Vilmen, Eric O. Freed |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
2019-20 coronavirus outbreak
Coronavirus disease 2019 (COVID-19) SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Acylation Virus Assembly S-acylation Spike Protein Golgi Apparatus Cell Biology Biology Preview Virology General Biochemistry Genetics and Molecular Biology COVID-19 Drug Treatment Membrane Lipids Humans Molecular Biology Acyltransferases Developmental Biology |
| Zdroj: | Developmental Cell |
| ISSN: | 1878-1551 1534-5807 |
| Popis: | SARS-CoV-2 virions are surrounded by a lipid bilayer that contains membrane proteins such as spike, responsible for target-cell binding and virus fusion. We found that during SARS-CoV-2 infection, spike becomes lipid modified, through the sequential action of the S-acyltransferases ZDHHC20 and 9. Particularly striking is the rapid acylation of spike on 10 cytosolic cysteines within the ER and Golgi. Using a combination of computational, lipidomics, and biochemical approaches, we show that this massive lipidation controls spike biogenesis and degradation, and drives the formation of localized ordered cholesterol and sphingolipid-rich lipid nanodomains in the early Golgi, where viral budding occurs. Finally, S-acylation of spike allows the formation of viruses with enhanced fusion capacity. Our study points toward S-acylating enzymes and lipid biosynthesis enzymes as novel therapeutic anti-viral targets. |
| Databáze: | OpenAIRE |
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