top of page
shivam kumar

S1 SPIKE protein that makes corona ( crown ) and binding to host cell major factor for infection


The spike protein (S protein) is a large type I transmembrane protein ranging from 1,160 amino acids for avian infectious bronchitis virus (IBV) and up to 1,400 amino acids for feline coronavirus (FCoV) (Figure 1). In addition, this protein is highly glycosylated as it contains 21 to 35 N-glycosylation sites. Spike proteins assemble into trimers on the virion surface to form the distinctive "corona", or crown-like appearance. The ectodomain of all CoV spike proteins share the same organization in two domains: a N-terminal domain named S1 that is responsible for receptor binding and a C-terminal S2 domain responsible for fusion (Figure 2). CoV diversity is reflected in the variable spike proteins (S proteins), which have evolved into forms differing in their receptor interactions and their response to various environmental triggers of virus-cell membrane fusion.

It's been reported that 2019-nCoV can infect the human respiratory epithelial cells through interaction with the human ACE2 receptor. Indeed, the recombinant


Spike protein can bind with recombinant ACE2 protein. A notable distinction between the spike proteins of different coronaviruses is whether it is cleaved or not during assembly and exocytosis of virions. With some exceptions, in most alphacoronaviruses and the betacoronavirus SARS-CoV, the virions harbor a spike protein that is uncleaved, whereas in some beta- and all gammacoronaviruses the protein is found cleaved between the S1 and S2 domains, typically by furin, a Golgi-resident host protease. Interestingly, within the betacoronavirus mouse hepatitis virus (MHV) species, different strains, such as MHV-2 and MHV-A59 display different cleavage requirements. This has important consequences on their fusogenicity.



SPIKE PROTEIN STRUCTURE :


The coronavirus spike protein is a class I fusion protein. The formation of an α-helical coiled-coil structure is characteristic of this class of fusion protein, which contain in their C-terminal part regions predicted to have an α-helical secondary structure and to form coiled-coils. The S2 subunit is the most conserved region of the protein, whereas the S1 subunit diverges in sequence even among species of a single coronavirus . The S1 contains two subdomains, a N-terminal domain (NTD) and a C-terminal domain (CTD). Both are able to function as receptor binding domains (RBDs) and bind variety of proteins and sugars.

Coronavirus spike proteins contain two heptad repeats in their S2 domain, a feature typical of a class I viral fusion proteins. Heptad repeats comprise a repetitive heptapeptide abcdefg with a and d being hydrophobic residues characteristic of the formation of coiled-coil that participate in the fusion process. For SARS-CoV and MHV, the post-fusion structures of the HR have been solved; they form the characteristic six-helix bundle. The functional role of MHV and SARS-CoV HR was confirmed by mutating key residues and by inhibition experiments using HR2 peptides.



S1 SPIKE distribution :


The CoVs are widely distributed in nature and their zoonotic transmissions into human populations can cause epidemic disease. After entering into respiratory or gastrointestinal tracts, these viruses establish themselves by entering and infecting lumenal macrophages and epithelial cells. The cell entry programs for these viruses are orchestrated by the viral spike (S) proteins that bind cellular receptors and also mediate virus-cell membrane fusions. Take SARS-CoV for example. The spike protein (S protein) of SARS-CoV has pivotal roles in viral infection and pathogenesis. S1 recognizes and binds to host receptors, and subsequent conformational changes in S2 facilitate fusion between the viral envelope and the host cell membrane.

Models depicting the S-mediated membrane fusion event have extended from knowledge of S protein structures and functions. In part, these models are deemed reasonable because the postfusion 6-HB conformations in SARS and MHV S proteins are so strikingly similar to postfusion forms of influenza HA2, paramyxovirus F2, cEbolavirus GP2 and HIV gp41. In analogy to these more widely-studied and well-understood viral fusion proteins .




15 views0 comments

Comments


bottom of page