Spike Protein

The amino acid sequences of S1 subunit of coronavirus S protein diverge across different genera but are relatively conserved within each genus. S1 contains two independent domains, an N-terminal domain (S1-NTD) and a C-terminal domain (S1-CTD, also called S1 C-domain) ^[3]. Coronaviruses have evolved a complex receptor recognition pattern: (i) either or both of these S1 domains can function as a receptor-binding domain (RBD) due to different Coronavirus. (ii) Highly similar coronavirus S1-CTDs within the same genus can recognize different protein receptors, whereas very different coronavirus S1-CTDs from different genera can recognize the same protein receptor; and (iii) coronavirus S1-NTDs can recognize either protein or sugar receptors. Understanding the receptor recognition mechanisms of coronaviruses can provide critical insight into the origin, evolution, and receptor selection of coronaviruses ^[4].

The binding interaction between coronavirus RBD and its receptor is one of the most important determinants of the coronavirus host range and cross-species infection. As for SARS-CoV and MERS-CoV, it is the S1-CTD plays the role of RBD, while the SARS-CoV S1-CTD binds to angiotensin-converting enzyme 2 (ACE2), and the MERS-CoV S1-CTD binds to dipeptidyl peptidase 4 (DPP4) ^[5].SARS-CoV-2 has the similar situation with SARS-CoV, the S1-CTD serves as the virus RBD.

Through amino acid (aa) sequence alignment with SARS-CoV and SARS-CoV-2 S protein, scientists have located the functional domain in the S1 subunit ((aa14–685) of SARS-CoV-2 S protein: N-terminal domain (aa14–305), receptor-binding domain (aa319–541), and receptor-binding motif (aa437–508).

Elabscience^® provides the RBD proteins of SARS-CoV-2 with different tags assisting your related research.

The S2 subunit of coronavirus S protein is responsible for membrane fusion during virus entry host cells. Amino acid sequence analysis has shown that the S2 subunit contains two tandem domains, heptad repeats 1 (HR1) and HR2, and it is more conserved than the S1 subunit among the CoVs. SARS-CoV S protein S2 subunit plays a key role in mediating virus fusion with and entry into the host cell, in which the heptad repeat 1 (HR1) and heptad repeat 2 (HR2) can interact to form six-helical bundle (6-HB), thereby bringing viral and cellular membranes in close proximity for fusion. However, it is unclear whether SARS-CoV-2 also possesses a similar fusion and entry mechanism as that of SARS-CoV and MERS-CoV, and if so, whether a SARS-CoV S-HR1 can also serve as an important target for the development of SARS-CoV fusion/entry inhibitors ^[6].

The latest research have located the functional domain in S2 subunit (aa686–1273): fusion peptide (aa788–806), HR1 (aa912–984), HR2 (aa1163–1213), transmembrane domain (aa1214–1237) and cytoplasm domain (aa1238–1273).