Cleavage of S protein into S1:S2

Stable Identifier
R-HSA-9686710
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
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Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.

Spike protein S2: Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.

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.

Within the host cell endocytic vesicle, SARS-CoV-1 Spike (S) protein is cleaved between residues 797 and 798 by cathepsin L1 (CTSL) (Huang et al. 2006). The roles of S protein in viral binding to the host cell membrane and fusion of viral and host cell membranes and thus the central role of S protein in determining the host range and tissue tropisms of the virus are reviewed by Belouzard et al. (2012).

Literature References
PubMed ID Title Journal Year
19321428 Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites

Belouzard, S, Chu, VC, Whittaker, GR

Proc. Natl. Acad. Sci. U.S.A. 2009
22816037 Mechanisms of coronavirus cell entry mediated by the viral spike protein

Belouzard, S, Millet, JK, Licitra, BN, Whittaker, GR

Viruses 2012
Participants
Participates
Catalyst Activity

serine-type endopeptidase activity of Cathepsin L1 [endocytic vesicle lumen]

This event is regulated
Orthologous Events
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
Authored
Reviewed
Created
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