SARS Spike Protein S2 (SARS S) Recombinant Protein

Function: S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.S2 is 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.

Subunit structure: Homotrimer. Binds to human and palm civet ACE2 and human CLEC4M/DC-SIGNR. Interacts with the accessory proteins 3a and 7a. Ref.22 Ref.23 Ref.26 Ref.27 Ref.32 Ref.33

Subcellular location: Virion membrane; Single-pass type I membrane protein. Host endoplasmic reticulum-Golgi intermediate compartment membrane; Single-pass type I membrane protein

By similarity. Host cell membrane; Single-pass type I membrane protein. Note: Accumulates in the endoplasmic reticulum-Golgi intermediate compartment, where it participates in virus particle assembly

By similarity. Some S oligomers are transported to the plasma membrane, where they may mediate cell-cell fusion. Ref.29

Domain: The KxHxx motif seems to function as an ER retrieval and binds COPI in vitro.

Post-translational modification: The cytoplasmic Cys-rich domain is palmitoylated. Spike glycoprotein is digested by cathepsin CTSL within endosomes. Ref.35

Miscellaneous: Tor2 is the prototype of the virus isolated during the severe SARS outbreak in 2002-2003. GD03 has been isolated from the second mild SARS outbreak in winter 2003-2004. SZ3 has been isolated from palm civet, the presumed animal reservoir. The spike proteins from those three isolates display a strong affinity for palm civet ACE2 receptor, whereas only the Tor2 spike protein efficiently binds human ACE2. This may explain the high pathogenicity of Tor2 virus, whose spike is highly adapted to the human host. Therefore, the lack of severity of disease during the 2003-2004 outbreak could be due to the incomplete adaptation of GD03 virus to bind human ACE2. Mutation Asn-479 and Thr-487 in palm civet coronavirus seems necessary and sufficient for the virus to acquire the ability to efficiently infect humans.

Sequence similarities: Belongs to the coronaviruses spike protein family.

Caution: Cleavage into S1 and S2 remains controversial, since biochemical evidence for this proteolytic cleavage is largely negative.