Abstract
Structural restraints in the SARS-CoV-2 spike tail control its intra-cellular trafficking to virion assembly and immune presentation sites
Biophysical journal, Vol.123(3_Supplement 1), pp.480a-481a
02/08/2024
DOI: 10.1016/j.bpj.2023.11.2918
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 an integrated crystallographic, NMR, single particle cryoEM, biophysical, and cellular 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 for incorporation into virions or export to the plasma membrane for cell-cell fusion and presentation to the host immune system. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly, fusogenicity, and immunogenic presentation, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation.
Details
- Title: Subtitle
- Structural restraints in the SARS-CoV-2 spike tail control its intra-cellular trafficking to virion assembly and immune presentation sites
- Creators
- Syed Saif Hasan - University of Maryland, BaltimoreDebajit Dey - University of Maryland, BaltimoreSuruchi Singh - University of Maryland, BaltimoreEnya Qing - Loyola University ChicagoYanan He - University of Maryland, College ParkYihong Chen - University of Maryland, College ParkBenjamin Jennings - Washington University in St. Louis School of MedicineWhitaker Cohn - University of California, Los AngelesLokesh Gakhar - PAQ Therapeutics, Cambridge, MA, USANicholas J. Schnicker - University of IowaBrian Pierce - University of Maryland, College ParkJulian Whitelegge - University of California, Los AngelesBalraj Doray - Washington University in St. Louis School of MedicineJohn P. Orban - University of Maryland, BaltimoreTom Gallagher - Loyola University Chicago
- Resource Type
- Abstract
- Publication Details
- Biophysical journal, Vol.123(3_Supplement 1), pp.480a-481a
- DOI
- 10.1016/j.bpj.2023.11.2918
- ISSN
- 0006-3495
- eISSN
- 1542-0086
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/08/2024
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration
- Record Identifier
- 9984631908202771
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