This domain is frequently found associated with the NACHT domain () in fish and other vertebrates []. Proteins containing this domain include NACHT, LRR and PYD domains-containing protein 3/12 (NLRP3/12). In humans, NLRP3 (also known as PYPAF1) may function as an inducer of apoptosis []. NLRP12 is a non-inflammasome NLR (nucleotide-binding domain and leucine-rich repeat-containing receptors) that has been implicated in the regulation of Toll-like receptor-dependent nuclear factor-kappaB activation [].
Coronavirus encodes two viroporins, E protein and protein 3a, which act as ion-conductive pores in planar lipid bilayers and are required for maximal SARS-CoV replication and virulence []. In betacoronavirus, this protein plays a role in viral egress via lysosomal trafficking [, ]. Protein 3a from SARS-CoV-2 also blocks autolysosomes formation by binding and sequestering the host component VPS39 for homotypic fusion and protein sorting (HOPS) on late endosomes. This prevents fusion of autophagosomes with lysosomes, disrupting autophagy and facilitating virus egress [].This entry represents protein 3a encoded by Orf3/3a, also known as X1, which forms homotetrameric potassium, sodium or calcium sensitive ion channels (viroporin) and may modulate virus release. It has also been shown to up-regulate expression of fibrinogen subunits FGA, FGBand FGG in host lung epithelial cells [, , , ].3a protein is a pro-apoptosis-inducing protein. It localises to the endoplasmic reticulum (ER)-Golgi compartment. SARS-CoV causes apoptosis of infected cells through NLRP3 inflammasome activation, as ORF3a is a potent activator of the signals required for this activation, pro-IL-1beta gene transcription and protein maturation. This protein also promotes the ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mediated by its interaction with TNF receptor-associated factor 3 (TRAF3). The expression of ORF3a induces NF-kappa B activation and up-regulates fibrinogen secretion with the consequent high cytokine production [, , , ]. Another apoptosis mechanism described for this protein is the activation of the PERK pathway of unfolded protein response (UPR), which causes phosphorylation of eIF2alpha and leads to reduced translation of cellular proteins as well as the activation of pro-apoptotic downstream effectors (i.e ATF4, CHOP) [].
This family is specific for E proteins from alphacoronaviruses.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 extramembranedomains, 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 [].
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 [].
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 [].
This entry represents the Envelope (E) small membrane protein of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV) or COVID-19 virus.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 [].
This entry represents the Envelope (E) small membrane protein of Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as E proteins from related coronaviruses.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 efficienttrafficking 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 [].
