Spike glycosylation and palmitoylation trafficking

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Glycosylation motifs and cysteine palmitoylation steer SARS-CoV-2 spike maturation, Golgi trafficking, and fusion.

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Glycosylation and S-palmitoylation regulate SARS-CoV-2 spike protein intracellular trafficking

Tien CF, Tsai WT, Chen CH, et al. · iScience · 2022

doi.org/10.1016/j.isci.2022.104709 Read the full paper ↗37 citationscc by

Study at a glance

Design: Animal / in-vitro — Mutagenesis and 2BP inhibition of SARS-CoV-2 spike glycosylation/palmitoylation trafficking
N: Cell-based spike trafficking/fusion assays — no single primary analytic N
Population: Cells expressing wild-type or mutant SARS-CoV-2 spike
Outcome: Spike intracellular trafficking, packaging, and ACE2-mediated fusion

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Spike glycosylation and palmitoylation trafficking

These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.

SARS-CoV-2 spike (S).

The SARS-CoV-2 spike (S) glycoprotein interacts with angiotensin-converting enzyme 2 (ACE2) on the cell surface during virus entry

Alanine substitutions (LYAA, AAQD, AAAA).

alanine substitution mutations in the LYQD sequence ( 611 LYAA 614 , 611 AAQD 614 , and 611 AAAA 614 ) were generated in

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What they did

Mutated LYQD and cysteine clusters in SARS-CoV-2 S, inhibited palmitoylation with 2BP, and tracked glycosylation, localization, packaging, and ACE2-mediated fusion.

What they found

LYQD mutants altered S2 glycosylation mobility; palmitoylation at cysteine clusters I/II was required for efficient S pp/virus production, Golgi/plasma-membrane targeting, and cell fusion.

The limits

What it doesn't show

Not a clinical antiviral trial; much work uses S pseudoviruses rather than full virus genetics for every assay.

Key terms

Spike (S): SARS-CoV-2 surface glycoprotein mediating entry.
Glycosylation: Sugar modification of the S glycoprotein.
Palmitoylation: Fatty-acyl modification of cysteine motifs.
2BP: 2-bromopalmitate palmitoylation inhibitor.
S pp: Spike-pseudotyped virus particles.
ACE2 fusion: Spike-driven membrane fusion with ACE2+ cells.

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Common questions

Key PTMs?

Glycosylation and palmitoylation.

Motif mutated?

LYQD.

Inhibitor?

2BP.

Trafficking target?

Golgi/plasma membrane.