A weak COPI binding motif in the cytoplasmic tail of SARS-CoV-2 spike glycoprotein is necessary for its cleavage, glycosylation, and localization.


Journal

FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157

Informations de publication

Date de publication:
07 2021
Historique:
revised: 26 04 2021
received: 07 04 2021
accepted: 10 05 2021
pubmed: 16 5 2021
medline: 15 7 2021
entrez: 15 5 2021
Statut: ppublish

Résumé

The SARS-CoV-2 spike glycoprotein (spike) mediates viral entry by binding ACE2 receptors on host cell surfaces. Spike glycan processing and cleavage, which occur in the Golgi network, are important for fusion at the plasma membrane, promoting both virion infectivity and cell-to-cell viral spreading. We show that a KxHxx motif in the cytosolic tail of spike weakly binds the COPβ' subunit of COPI coatomer, which facilitates some recycling of spike within the Golgi, while releasing the remainder to the cell surface. Although histidine (KxHxx) has been proposed to be equivalent to lysine within di-lysine endoplasmic reticulum (ER) retrieval sequences, we show that histidine-to-lysine substitution (KxKxx) retains spike at the ER and prevents glycan processing, protease cleavage, and transport to the plasma membrane.

Identifiants

pubmed: 33991349
doi: 10.1002/1873-3468.14109
pmc: PMC8209879
mid: NIHMS1704941
doi:

Substances chimiques

Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0
Histidine 4QD397987E
Lysine K3Z4F929H6

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1758-1767

Subventions

Organisme : NCI NIH HHS
ID : R01 CA008759
Pays : United States

Informations de copyright

© 2021 Federation of European Biochemical Societies.

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Auteurs

Benjamin C Jennings (BC)

Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Stuart Kornfeld (S)

Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Balraj Doray (B)

Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

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Classifications MeSH