| Theoretical Model:
The protein structure described on this page was determined theoretically, and hence should be interpreted with caution. |
Function
Surface glycoprotein (S)
The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in the type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell.(Wikipedia).
Complex Spine S protein and ACE2
Spine S protein
Spike protein S1 (residue 14-685): attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.
Spike protein S2 (residue 686-1273): 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' (residue 816-1273): acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[1][2]
Disease
Relevance
Structural highlights
See also
Coronavirus_Disease 2019 (COVID-19)
