Journal article
A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs
Nature communications, Vol.14(1), pp.8358-8358
12/15/2023
DOI: 10.1038/s41467-023-44076-3
PMCID: PMC10724246
PMID: 38102143
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 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.
Details
- Title: Subtitle
- A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs
- Creators
- Debajit Dey - University of Maryland, BaltimoreEnya Qing - Loyola University ChicagoYanan He - Advanced Bioscience LaboratoriesYihong Chen - Advanced Bioscience LaboratoriesBenjamin Jennings - Washington University in St. LouisWhitaker Cohn - University of California, Los AngelesSuruchi Singh - University of Maryland, BaltimoreLokesh Gakhar - University of IowaNicholas J Schnicker - University of IowaBrian G Pierce - Advanced Bioscience LaboratoriesJulian P Whitelegge - University of California, Los AngelesBalraj Doray - Washington University in St. LouisJohn Orban - Advanced Bioscience LaboratoriesTom Gallagher - Loyola University ChicagoS Saif Hasan - University of Maryland, Baltimore
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.14(1), pp.8358-8358
- DOI
- 10.1038/s41467-023-44076-3
- PMID
- 38102143
- PMCID
- PMC10724246
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- R01 GM150187 / NIGMS NIH HHS P30 CA134274 / NCI NIH HHS P01 AI060699 / NIAID NIH HHS R01 CA008759 / NCI NIH HHS
- Language
- English
- Date published
- 12/15/2023
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration
- Record Identifier
- 9984622756702771
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