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Coronavirus Envelope (E) small membrane protein This family contains the Envelope (E) small membrane protein of betacoronaviruses, including the E proteins from three highly pathogenic human coronaviruses (CoVs) such as Middle East respiratory syndrome (MERS) CoV, Severe acute respiratory syndrome (SARS) CoV, and SARS-CoV-2, also known as 2019 novel CoV (2019-nCoV) or COVID-19 virus. There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and the Orf1ab (a large polyprotein known as replicase/protease); all are required to produce a structurally complete viral particle. The E protein is a small polypeptide (76-109 amino acids) that contains a single alpha-helical transmembrane domain. It plays a central role in virus morphogenesis and assembly. It acts as a viroporin and self-assembles in host membranes forming homopentameric protein-lipid pores that allow ion transport with poor selectivity. For some CoVs, such as mouse hepatitis virus (MHV) and SARS-CoV, deletion of the E gene did not completely abolish replication, but the virions were severely disabled from infecting new host cells with significantly reduced viral titers. In animal models, SARS-CoV lacking the E gene also showed significantly attenuated viral titers, likely due to its deficiency in suppressing host stress response and apoptosis induction. Moreover, the PDZ-binding motif (PBM) at the C-terminus of SARS-CoV E protein was shown to interact with a host PDZ protein called syntenin and lead to its relocation from nucleus to cytoplasm during SARS-CoV infection, thereby activating p38 kinase to induce the overexpression of inflammatory cytokines. Thus, the E protein is involved in both, viral replication and pathogenesis during CoV infection. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",