8t7a

Structural highlights

Function

FUS_HRSV Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins.[UniProtKB:P03420] Class I viral fusion protein. 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. 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. 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. This fusion is pH independent and occurs at the plasma or endosomal membrane. The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate. F protein is involved in the entry into the host cell through the interaction with host IGF1R. This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1. 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. F protein may trigger p53-dependent apoptosis.[UniProtKB:P03420] Major determinant of the species specificity of RSV infection. The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate. F protein is involved in the entry into the host cell through the interaction with host IGF1R. This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1. 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. F protein seems to trigger p53-dependent apoptosis.[UniProtKB:P03420]

References

1. ↑ McCool RS, Musayev M, Bush SM, Derrien-Colemyn A, Acreman CM, Wrapp D, Ruckwardt TJ, Graham BS, Mascola JR, McLellan JS. Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein elicits antibodies targeting a membrane-proximal epitope. J Virol. 2023 Sep 22:e0092923. PMID:37737588 doi:10.1128/jvi.00929-23