Envelope Protein
Envelope Protein of Coronavirus
The envelope protein (E protein), along with nucleocapsid protein (N protein), spike protein (S protein), and membrane protein (M protein), are the major coronavirus structural proteins. CoV E protein is a small (76–109 amino acids) integral membrane protein, and has a single predicted hydrophobic domain (HD). It is usually encoded as the second or third message in a bi- or tri-cistronic mRNA [1].
The E protein is targeted to the Golgi region in infected cells and also when expressed from cDNA. The membrane topology of CoV E is of considerable debate, having been reported as transmembrane or a membrane hairpin. There are conserved membrane proximal cysteine residues that are targets for palmitoylation [2,3]. There are also conserved proline residues in the C-terminal tail. Other than these similarities there is large variation in the primary sequence of the E proteins, which differ in size and sequence among virus groups often having <30% identity.How or if these differences affect protein function is not known.
The CoV E protein has a well-established role in the assembly of virions where it may induce membrane curvature or aid in membrane scission. Recent studies have expanded the role of CoV E beyond assembly. CoV E has ion channel activity in vitro. CoV E also is critical for the efficient trafficking of virions through the secretory pathway, a function that may be related to its ion channel activity. The CoV E protein has recently been shown to inhibit the host cell stress response, implicating it in pathogenesis. New interacting partners for E have been identified that expand the role of the protein during infection [4].
The CoV E protein is an enigmatic protein. There is a high degree of variability in the behavior of the E proteins from different CoVs, including their requirement for assembly, virion trafficking, ion channel function, and method of expression in the genome. Yet, this protein is present in all known CoVs, suggesting it has a conserved role. It is interesting to speculate that the E protein from different CoVs has evolved to perform different functions. This could be due to cell-type specific requirements for each virus, or the ability of an accessory protein to complement a function normally carried out by E. Understanding how the E proteins from different CoVs vary is a crucial step in elucidating the mechanism of CoV assembly and egress.
Primary structure of the Coronavirus (CoV) E protein [4]. (A) A cartoon depicting a CoV virion. (B) The three major CoV structural proteins in the virion envelope. (C) A multiple sequence alignment of several different CoV E proteins. (D) Cartoon depiction of the E protein with the hydrophobic domain shown as a cylinder and the conserved Cys and Pro residues labeled.
Reference
- 1.Boursnell M.E., Binns M.M., Brown T.D. Sequencing of coronavirus IBV genomic RNA: Three open reading frames in the 5' 'unique' region of mRNA D. J. Gen. Virol. 1985;66:2253–2258.
- 2.Corse E., Machamer C.E. Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles. J. Virol. 2000;74:4319–4326.
- 3.Liao Y., Yuan Q., Torres J., Tam J.P., Liu D.X. Biochemical and functional characterization of the membrane association and membrane permeabilizing activity of the severe acute respiratory syndrome coronavirus envelope protein. Virology. 2006;349:264–275.
- 4. Ruch TR, Machamer CE. The coronavirus E protein: assembly and beyond. Viruses. 2012;4(3):363‐382.