The following text describes a protein:
Function:
[Spike protein S1]: Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. The major receptor is host ACE2. When S2/S2' has been cleaved, binding to the receptor triggers direct fusion at the cell membrane. When S2/S2' has not been cleaved, binding to the receptor results in internalization of the virus by endocytosis using host TFRC and GRM2 and leading to fusion of the virion membrane with the host endosomal membrane. Alternatively, may use NRP1/NRP2 and integrin as entry receptors. The use of NRP1/NRP2 receptors may explain the tropism of the virus in human olfactory epithelial cells, which express these molecules at high levels but ACE2 at low levels. The stalk domain of S contains three hinges, giving the head unexpected orientational freedom; [Spike protein S2]: Precursor of the fusion protein processed in the biosynthesis of the S protein and the formation of virus particle. Mediates fusion of the virion and cellular membranes by functioning as a class I viral fusion protein. Contains two viral fusion peptides that are unmasked after cleavage. The S2/S2' cleavage occurs during virus entry at the cell membrane by host TMPRSS2 or during endocytosis by host CSTL. In either case, this triggers an extensive and irreversible conformational change leading to fusion of the viral envelope with the cellular cytoplasmic membrane, releasing viral genomic RNA into the host cell cytoplasm. 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 fusion of the viral and target cell membranes, the coiled coil regions (heptad repeats) adopt a trimer-of-hairpins structure and position the fusion peptide in close proximity to the C-terminal region of the ectodomain. Formation of this structure appears to promote apposition and subsequent fusion of viral and target cell membranes; [Spike protein S2']: Subunit of the fusion protein that is processed upon entry into the host cell. Mediates fusion of the virion and cellular membranes by functioning as a class I viral fusion protein. Contains a viral fusion peptide that is unmasked after S2 cleavage. This cleavage can occur at the cell membrane by host TMPRSS2 or during endocytosis by host CSTL. In either case, this triggers an extensive and irreversible conformational change that leads to fusion of the viral envelope with the cellular cytoplasmic membrane, releasing viral genomic RNA into the host cell cytoplasm. 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 fusion of the viral and target cell membranes, the coiled coil regions (heptad repeats) adopt a trimer-of-hairpins structure and position the fusion peptide in close proximity to the C-terminal region of the ectodomain. Formation of this structure appears to promote apposition and subsequent fusion of viral and target cell membranes.
Miscellaneous:
MISCELLANEOUS: Variant D614G has become the most prevalent circulating sequence in the global pandemic since April 2020. The mutation is associated with higher viral loads produced in cell culture and animal models. It would not change pathogenicity nor neutralization properties vs vaccination. May be prevalent because the mutation increases virus transmission in human population.
Subcellular 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. Note=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. An average of 26 +/-15 S trimers are found randomly distributed at the surface of the virion.
Domain:
Contains sequence and structural motifs very similar to those of a bacterial superantigen and can directly bind and activate T-cell receptors. Activation of a broad T-cell repertoire may be involved in the hyperinflammatory syndrome in acute COVID disease; The KxHxx motif seems to function as an ER retrieval and binds COPI in vitro; 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.
Sequence:
MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT