| Primary Identifier | IPR043506 | Type | Family |
| Short Name | E_protein_bCoV |
| description | This family is specific for E proteins from betacoronaviruses.E protein is the smallest of the major structural proteins. It is conserved among Coronavirus strains. It is an integral membrane protein involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis []. During the replication cycle, E is abundantly expressed inside the infected cell, but only a small portion is incorporated into the virus envelope. The majority of the protein participates in viral assembly and budding [, ]. It can act as a viroporin by oligomerizing after insertion in host membranes to create a hydrophilic pore that allows ion transport [, ]. Additionally, the E protein is thought to prevent M protein aggregation and induce membrane curvature [].SARS-CoV E protein forms a Ca2+ permeable channel in the endoplasmic reticulum Golgi apparatus intermediate compartment (ERGIC)/Golgi membranes. The E protein ion channel activity alters Ca2+ homeostasis within cells boosting the activation of the NLRP3 inflammasome, which leads to the overproduction of IL-1beta. SARS-CoV overstimulates the NF-kappaB inflammatory pathway and interacts with the cellular protein syntenin, triggering p38 MARK activation. These signalling cascades result in exacerbated inflammation and immunopathology [].Cov E proteins have a short hydrophilic N terminus, followed by a large hydrophobic transmembrane (TM) domain, and end with a long, hydrophilic C terminus, which comprises the majority of the protein. The hydrophobic region of the TM domain contains at least one predicted amphipathic α-helix that pentamerizes to form an ion-conductive pore in membranes. CoV E proteins have been proposed to have at least two roles. One is related to their TM channel domain. This would be active in the secretory pathway, altering lumenal environments and rearranging secretory organelles and leading to efficient trafficking of virions. The other would be related to their extramembrane domains, particularly the C-terminal domain. This is involved in protein-protein interactions and targeting, among other roles [, , , ]. In the CoV E protein structure a longer α-helix encompasses the TM domain, which is connected to another shorter C-terminal α-helix by a flexible linker domain, forming an L-shape [Li]. The CoV E pentamer is a right handed α-helical bundle where the C-terminal tails coil around each other []. |
