F
Domain
Fusion glycoprotein F0
The N-terminus is a hydrophobic fusion peptide that inserts into the target host membrane (By similarity). It is buried in the center of the trimer cavity before cleavage by host furin (PubMed:23618766). The coiled coil (heptad repeat) regions are probably involved in homotrimerization, heterodimerization and in the formation of a fusion-active hairpin structure (PubMed:10846072, PubMed:29212939).
Fusion glycoprotein F1
The N-terminus is a hydrophobic fusion peptide that inserts into the target host membrane (By similarity). It is buried in the center of the trimer cavity before cleavage by host furin (PubMed:23618766). The coiled coil (heptad repeat) regions are probably involved in homotrimerization, heterodimerization and in the formation of a fusion-active hairpin structure (PubMed:10846072).
Function
Fusion glycoprotein F0
Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins.
Fusion glycoprotein F1
Class I viral fusion protein (PubMed:23618766). Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state (PubMed:23618766). During viral and plasma cell membrane fusion, the coiled coil regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain (PubMed:19966279, PubMed:23618766). The formation of this structure appears to drive apposition and subsequent fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm (PubMed:23593008, PubMed:23618766). This fusion is pH independent and occurs at the plasma or endosomal membrane (Probable). The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate (PubMed:10864656). F protein is involved in the entry into the host cell through the interaction with host IGF1R (PubMed:32494007). This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1 (PubMed:21841784, PubMed:32494007). Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (PubMed:10438814). F protein may trigger p53-dependent apoptosis (PubMed:18216092).
Fusion glycoprotein F2
Major determinant of the species specificity of RSV infection (PubMed:12663767). The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate (PubMed:10864656). F protein is involved in the entry into the host cell through the interaction with host IGF1R (PubMed:32494007). This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1 (PubMed:32494007). Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (PubMed:10438814). F protein seems to trigger p53-dependent apoptosis (PubMed:18216092).
Post-translational modifications
Fusion glycoprotein F0
The F glycoprotein is synthesized as a F0 inactive precursor that is heavily N-glycosylated and processed at two sites by a host furin-like protease probably in the Golgi (PubMed:11369882, PubMed:11418598, PubMed:11493675, PubMed:23593008). The cleavage site between p27 and F1 may occur after endocytosis to yield the mature F1 and F2 proteins (Probable). Both cleavages are required for membrane fusion and p27 is released from the processed protein (PubMed:11493675, PubMed:12127793, PubMed:23593008).
Sequence Similarities
Belongs to the paramyxoviruses fusion glycoprotein family.
Cellular localization
- Fusion glycoprotein F0
- Host Golgi apparatus membrane
- Single-pass membrane protein
- Fusion glycoprotein F1
- Virion membrane
- Single-pass type I membrane protein
- Host cell membrane
- Single-pass membrane protein
- Localized at the host apical membrane.
- Fusion glycoprotein F2
- Virion membrane
- Host cell membrane
- Localized at the host apical membrane.
Alternative names
Fusion glycoprotein F0, F