A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs
© 2023. The Author(s)..
The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly and fusogenicity, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 15. Dez., Seite 8358 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dey, Debajit [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 18.12.2023 Date Revised 31.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-44076-3 |
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| Förderinstitution / Projekttitel: |
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NLM365928348 |
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| 245 | 1 | 2 | |a A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly and fusogenicity, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation | ||
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| 700 | 1 | |a Qing, Enya |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yanan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yihong |e verfasserin |4 aut | |
| 700 | 1 | |a Jennings, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Cohn, Whitaker |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Suruchi |e verfasserin |4 aut | |
| 700 | 1 | |a Gakhar, Lokesh |e verfasserin |4 aut | |
| 700 | 1 | |a Schnicker, Nicholas J |e verfasserin |4 aut | |
| 700 | 1 | |a Pierce, Brian G |e verfasserin |4 aut | |
| 700 | 1 | |a Whitelegge, Julian P |e verfasserin |4 aut | |
| 700 | 1 | |a Doray, Balraj |e verfasserin |4 aut | |
| 700 | 1 | |a Orban, John |e verfasserin |4 aut | |
| 700 | 1 | |a Gallagher, Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Hasan, S Saif |e verfasserin |4 aut | |
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