Coronavirus envelope protein
| Envelope protein | |||||||||
|---|---|---|---|---|---|---|---|---|---|
virion[1]
● Blue: envelope ● Turquoise: spike glycoprotein (S) ● Bright Pink: envelope proteins (E) ● Green: membrane proteins (M) ● Orange: glycans | |||||||||
| Identifiers | |||||||||
| Symbol | CoV_E | ||||||||
| Pfam | PF02723 | ||||||||
| InterPro | IPR003873 | ||||||||
| PROSITE | PS51926 | ||||||||
| |||||||||
The envelope (E) protein is the smallest and least well-characterized of the four major
viral capsid, it is thought to be involved in viral assembly, likely functions as a viroporin, and is involved in viral pathogenesis.[2][5]
Structure
The E protein consists of a short
conserved only in the alpha and beta coronavirus groups, but not gamma.[2] In the beta and gamma groups, a conserved proline residue is found in the C-terminal region likely involved in targeting the protein to the Golgi.[2]
The transmembrane helices of the E proteins of SARS-CoV and SARS-CoV-2 can
cation-selective ion channels.[5] Both viruses' E protein pentamers have been structurally characterized by nuclear magnetic resonance spectroscopy.[5][7]
The membrane topology of the E protein has been studied in a number of coronaviruses with inconsistent results; the protein's orientation in the membrane may be variable.[3] The balance of evidence suggests the most common orientation has the C-terminus oriented toward the cytoplasm.[8] Studies of SARS-CoV-2 E protein are consistent with this orientation.[5][9]
Post-translational modifications
In some, but not all, coronaviruses, the E protein is
Ubiquitination of SARS-CoV E has also been described, though its functional significance is also not known.[2]
Expression and localization
Genomic organisation of isolate Wuhan-Hu-1, the earliest sequenced sample of SARS-CoV-2, indicating the location of the E gene | |
| NCBI genome ID | 86693 |
|---|---|
| Genome size | 29,903 bases |
| Year of completion | 2020 |
| Genome browser (UCSC) | |
The E protein is
virions.[2][4] E protein is localized to the endoplasmic reticulum, Golgi apparatus, and endoplasmic-reticulum–Golgi intermediate compartment (ERGIC), the intracellular compartment that gives rise to the coronavirus viral envelope.[2][5]
Function
Essentiality
Studies in different coronaviruses have reached different conclusions about whether E is
viral titer,[12] in some cases by introducing propagation defects or causing abnormal capsid morphology.[2]
Virions and viral assembly
respiratory mucosa, showing the positions of the four structural proteins and components of the extracellular environment[13]
The E protein is found in assembled virions where it forms
viral budding or scission, although its role in this process has not been well characterized.[2][4][15]
Viroporin
In its
cation-selective ion channels and likely functions as a viroporin.[5] NMR studies show that viroporin presents an open conformation at low pH or in the presence of calcium ions, while the closed conformation is favored at basic pH.[16] The NMR structure shows a hydrophobic gate at leucine 28 in the middle of the pore. The passage of ions through the gate is thought to be facilitated by the polar residues at the C-terminus.[17]
The cation leakage may disrupt ion
The E protein's role as a viroporin appears to be involved in
animal models despite little effect on viral growth.[10]
Interactions with host proteins
Cryo-electron microscopy structure of the interaction between the SARS-CoV-2 E protein PDZ-binding motif (magenta) and a construct containing the PDZ (blue), SH3 (yellow), and guanylate kinase-like (GK, green) domains from a host cell protein, human PALS1[19]
SARS-CoV and occur via the C-terminal PDZ domain binding motif. The SARS-CoV E protein has been reported to interact with five host cell proteins: Bcl-xL, PALS1, syntenin, sodium/potassium (Na+/K+) ATPase α-1 subunit, and stomatin.[2] The interaction with PALS1 may be related to pathogenesis via the resulting disruption in tight junctions.[3][10] This interaction has also been identified in SARS-CoV-2.[19]
Evolution and conservation
The sequence of the E protein is not well
deletion.[4] A study of SARS-CoV-2 sequences suggests that the E protein is evolving relatively slowly compared to other structural proteins.[21] The conserved nature of the envelope protein among SARS-CoV and SARS-CoV-2 variants has led it to be researched as a potential target for universal coronavirus vaccine development.[22][23]
References
- ^ Solodovnikov, Alexey; Arkhipova, Valeria (2021-07-29). "Достоверно красиво: как мы сделали 3D-модель SARS-CoV-2" [Truly beautiful: how we made the SARS-CoV-2 3D model] (in Russian). N+1. Archived from the original on 2021-07-30. Retrieved 30 July 2021.
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