S
Domain
Fusion peptide 1 (FP1) and fusion peptide 2 (FP2) function cooperatively and have a membrane-ordering effect on lipid headgroups and shallow hydrophobic regions of target bilayers. They are considered as two domains of an extended, bipartite FP. The membrane-ordering activity is calcium-dependent and also dependent on correct folding, which is maintained by an internal disulfide bond in FP2.
Function
Spike protein S1
Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.
Spike protein S2
Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.
Spike protein S2'
Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.
Post-translational modifications
Specific enzymatic cleavages in vivo yield mature proteins. The precursor is processed into S1 and S2 by host cell furin or another cellular protease to yield the mature S1 and S2 proteins. Additionally, a second cleavage leads to the release of a fusion peptide after viral attachment to host cell receptor.
The cytoplasmic Cys-rich domain is palmitoylated. Spike glycoprotein is digested within host endosomes.
Sequence Similarities
Belongs to the betacoronaviruses spike protein family.
Cellular localization
- Virion membrane
- Single-pass type I membrane protein
- Host endoplasmic reticulum-Golgi intermediate compartment membrane
- Single-pass type I membrane protein
- Host cell membrane
- Single-pass type I membrane protein
- Accumulates in the endoplasmic reticulum-Golgi intermediate compartment, where it participates in virus particle assembly. Some S oligomers are transported to the host plasma membrane, where they may mediate cell-cell fusion.
Alternative names
3, S, Spike glycoprotein, S glycoprotein, E2, Peplomer protein