A single C-terminal residue controls SARS-CoV-2 spike trafficking and virion assembly
ABSTRACT 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 cells1-3. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virions and viral 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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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 13. März Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dey, Debajit [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.03.09.531992 |
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| PPN (Katalog-ID): |
XBI038918382 |
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| 245 | 1 | 0 | |a A single C-terminal residue controls SARS-CoV-2 spike trafficking and virion assembly |
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| 520 | |a ABSTRACT 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 cells1-3. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virions and viral 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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Qing, Enya |4 aut | |
| 700 | 1 | |a He, Yanan |4 aut | |
| 700 | 1 | |a Chen, Yihong |4 aut | |
| 700 | 1 | |a Jennings, Benjamin |4 aut | |
| 700 | 1 | |a Cohn, Whitaker |4 aut | |
| 700 | 1 | |a Singh, Suruchi |4 aut | |
| 700 | 1 | |a Gakhar, Lokesh |4 aut | |
| 700 | 1 | |a Schnicker, Nicholas J. |4 aut | |
| 700 | 1 | |a Pierce, Brian G. |4 aut | |
| 700 | 1 | |a Whitelegge, Julian P. |4 aut | |
| 700 | 1 | |a Doray, Balraj |4 aut | |
| 700 | 1 | |a Orban, John P. |4 aut | |
| 700 | 1 | |a Gallagher, Tom |4 aut | |
| 700 | 1 | |a Hasan, S. Saif |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 13. März |
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