Coronavirus spike protein
Spike (S) glycoprotein (sometimes also called spike protein,[2] formerly known as E2[3]) is the largest of the four major structural proteins found in coronaviruses.[4] The spike protein assembles into trimers that form large structures, called spikes or peplomers,[3] that project from the surface of the virion.[4][5] The distinctive appearance of these spikes when visualized using negative stain transmission electron microscopy, "recalling the solar corona",[6] gives the virus family its main name.[2]
Coronavirus spike glycoprotein
The function of the spike glycoprotein is to mediate viral entry into the host cell by first interacting with molecules on the exterior cell surface and then fusing the viral and cellular membranes. Spike glycoprotein is a class I fusion protein that contains two regions, known as S1 and S2, responsible for these two functions. The S1 region contains the receptor-binding domain that binds to receptors on the cell surface. Coronaviruses use a very diverse range of receptors; SARS-CoV (which causes SARS) and SARS-CoV-2 (which causes COVID-19) both interact with angiotensin-converting enzyme 2 (ACE2). The S2 region contains the fusion peptide and other fusion infrastructure necessary for membrane fusion with the host cell, a required step for infection and viral replication. Spike glycoprotein determines the virus' host range (which organisms it can infect) and cell tropism (which cells or tissues it can infect within an organism).[4][5][7][8]
Spike glycoprotein is highly immunogenic. Antibodies against spike glycoprotein are found in patients recovered from SARS and COVID-19. Neutralizing antibodies target epitopes on the receptor-binding domain.[9] Most COVID-19 vaccine development efforts in response to the COVID-19 pandemic aim to activate the immune system against the spike protein.[10][11][12]
Betacoronavirus spike glycoprotein S1, receptor binding
bCoV_S1_RBD
bCoV_S1_N
CoV_S2
29,903 bases
2020
Evolution, conservation and recombination[edit]
The class I fusion proteins, a group whose well-characterized examples include the coronavirus spike protein, influenza virus hemagglutinin, and HIV Gp41, are thought to be evolutionarily related.[7][88] The S2 region of the spike protein responsible for membrane fusion is more highly conserved than the S1 region responsible for receptor interactions.[4][5][7] The S1 region appears to have undergone significant diversifying selection.[89]
Within the S1 region, the N-terminal domain (NTD) is more conserved than the C-terminal domain (CTD).[7] The NTD's galectin-like protein fold suggests a relationship with structurally similar cellular proteins from which it may have evolved through gene capture from the host.[7] It has been suggested that the CTD may have evolved from the NTD by gene duplication.[7] The surface-exposed position of the CTD, vulnerable to the host immune system, may place this region under high selective pressure.[7] Comparisons of the structures of different coronavirus CTDs suggests they may be under diversifying selection[90] and in some cases, distantly related coronaviruses that use the same cell-surface receptor may do so through convergent evolution.[14]