Structural highlights
Function
POLSF_SFV Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers (By similarity). The capsid protein binds to the viral RNA genome at a site adjacent to a ribosome binding site for viral genome translation following genome release (By similarity). Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein (By similarity). 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 icosahedric core particles (By similarity). The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions (By similarity). In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane (By similarity). This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible (By similarity). The uncoating might be triggered by the interaction of capsid proteins with ribosomes (By similarity). Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding (By similarity). Specifically inhibits interleukin-1 receptor-associated kinase 1/IRAK1-dependent signaling during viral entry, representing a means by which the alphaviruses may evade innate immune detection and activation prior to viral gene expression (By similarity).[UniProtKB:P03315][UniProtKB:P03316][UniProtKB:P27284] Provides the signal sequence for p62 (E3/E2) translocation to the host endoplasmic reticulum. Mediates pH protection of E1 during secretory pathway trans- port.[1] Plays a role in 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.[2] Virion component that may play a role during viral assembly.[3]
References
- ↑ Uchime O, Fields W, Kielian M. The role of E3 in pH protection during alphavirus assembly and exit. J Virol. 2013 Sep;87(18):10255-62. PMID:23864626 doi:10.1128/JVI.01507-13
- ↑ Kail M, Hollinshead M, Ansorge W, Pepperkok R, Frank R, Griffiths G, Vaux D. The cytoplasmic domain of alphavirus E2 glycoprotein contains a short linear recognition signal required for viral budding. EMBO J. 1991 Sep;10(9):2343-51. PMID:1714373 doi:10.1002/j.1460-2075.1991.tb07773.x
- ↑ Firth AE, Chung BY, Fleeton MN, Atkins JF. Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma. Virol J. 2008 Sep 26;5:108. PMID:18822126 doi:10.1186/1743-422X-5-108
