A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs.

Autor: Dey D; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Qing E; Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL, 60153, USA., He Y; University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA., Chen Y; University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA., Jennings B; Department of Internal Medicine, Hematology Division, Washington University School of Medicine, St. Louis, MO, 63110, USA., Cohn W; Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Singh S; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Gakhar L; Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.; Protein and Crystallography Facility, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.; PAQ Therapeutics, Burlington, MA, 01803, USA., Schnicker NJ; Protein and Crystallography Facility, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.; Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA., Pierce BG; University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA., Whitelegge JP; Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Doray B; Department of Internal Medicine, Hematology Division, Washington University School of Medicine, St. Louis, MO, 63110, USA., Orban J; University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.; Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA., Gallagher T; Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL, 60153, USA., Hasan SS; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. sshasan@som.umaryland.edu.; University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical Center, Baltimore, MD, 21201, USA. sshasan@som.umaryland.edu.; Center for Biomolecular Therapeutics, University of Maryland School of Medicine, Rockville, MD, 20850, USA. sshasan@som.umaryland.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Dec 15; Vol. 14 (1), pp. 8358. Date of Electronic Publication: 2023 Dec 15.
DOI: 10.1038/s41467-023-44076-3
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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