UniProtKB/Swiss-Prot entry P03315

• FUNCTION: Capsid protein possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosaedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of E2 at the cell membrane, leading to budding and formation of mature virions. New virions attach to target cells, and after endocytosis their membrane fuses with the target cell membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding.
• FUNCTION: E3 protein's function is unknown.
• FUNCTION: E2 is responsible for viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane.
• FUNCTION: 6K is a constitutive membrane protein involved in virus glycoprotein processing, membrane permeabilization, and the budding of viral particles. Present in low amount in virions, about 3% compared to viral glycoproteins. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds.
• FUNCTION: E1 is a class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after cell and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.
• SUBUNIT: p62 and E1 form a heterodimer shortly after synthesis. Processing of p62 into E2 and E3 results in a heterodimer of E2 and E1. Spike at virion surface are constituted of three E2-E1 heterodimers. After target cell attachment and endocytosis, E1 change conformation to form homotrimers.
• SUBCELLULAR LOCATION: Capsid protein: Virion (By similarity). Cytoplasm (By similarity).
• SUBCELLULAR LOCATION: p62: Virion membrane; Single-pass type I membrane protein (By similarity). Cell membrane; Single-pass type I membrane protein (By similarity).
• SUBCELLULAR LOCATION: E2 envelope glycoprotein: Virion membrane; Single-pass type I membrane protein (By similarity). Cell membrane; Single-pass type I membrane protein (By similarity).
• SUBCELLULAR LOCATION: E1 envelope glycoprotein: Virion membrane; Single-pass type I membrane protein (By similarity). Cell membrane; Single-pass type I membrane protein (By similarity).
• SUBCELLULAR LOCATION: 6K protein: Cell membrane; Multi-pass membrane protein (By similarity). Virion membrane; Multi-pass membrane protein (By similarity).
• PTM: Specific enzymatic cleavages in vivo yield mature proteins. Capsid protein is auto-cleaved during polyprotein translation, unmasking p62 signal peptide. The remaining polyprotein is then targeted to the endoplasmic reticulum, where host signal peptidase cleaves it into p62, 6K and E1 proteins. p62 is further processed to mature E3 and E2 by host furin in trans-Golgi vesicle. Protein processing process takes about 30 minutes at physiologic temperatures. The folding of the p62/6K/E1 precursor requires the formation of intrachain disulfide bonds and has been shown to involve a transient covalent interaction between the nascent and newly synthesized heterodimer and the host-cell chaperones, P4HB/PDI and PDIA3/ERp57. The folding pathway also includes non covalent interaction with human CANX/calnexin and CALR/calreticulin.
• PTM: Envelope E1, E2 and E3 proteins are N-glycosylated.
• PTM: E2 is palmitoylated via thioester bonds. These palmitoylations may induce disruption of the C-terminus transmembrane. This would result in the reorientation of E2 c-terminus from lumenal to cytoplasmic side. 6K protein is also palmitoylated with about four covalently bound fatty acids per molecule. E1 is stearoylated.
• MISCELLANEOUS: The mature virion nucleocapsid consists of 240 copies of the capsid protein. 80 spike trimers of E1 and E2 are present at the surface of mature virion. They project about 100 Angstroms from the outer surface and are located at the local and strict three fold axis of the icosaedral lattice. The glycoproteins splay out to form a protein shell or skirt covering most of the outer surface of the membrane bilayer.
• MISCELLANEOUS: Structural polyprotein is translated from a subgenomic RNA synthesized during togavirus replication.
• SIMILARITY: Contains 1 peptidase S3 domain [view classification].
• WEB RESOURCE: Name=Virus Particle ExploreR db; Note= Icosahedral capsid structure; URL="http://viperdb.scripps.edu/info_page.php?VDB=1dwn";.