Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/9952
Cleavage of the human respiratory syncytial virus fusion protein at two distinct sites is required for activation of membrane fusion
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9859-64
Preparations of purified full-length fusion (F) protein of human respiratory syncytial virus (HRSV) expressed in recombinant vaccinia-F infected cells, or of an anchorless mutant (F(TM(-))) lacking the C-terminal 50 amino acids secreted from vaccinia-F(TM(-))-infected cells contain a minor polypeptide that is an intermediate product of proteolytic processing of the F protein precursor F0. N-terminal sequencing of the intermediate demonstrated that it is generated by cleavage at a furin-motif, residues 106-109 of the F sequence. By contrast, the F1 N terminus derives from cleavage at residue 137 of F0 which is also C-terminal to a furin recognition site at residues 131-136. Site-directed mutagenesis indicates that processing of F0 protein involves independent cleavage at both sites. Both cleavages are required for the F protein to be active in membrane fusion as judged by syncytia formation, and they allow changes in F structure from cone- to lollipop-shaped spikes and the formation of rosettes by anchorless F.
Amino Acid Motifs | Amino Acid Sequence | Animals | Cell Line | Cricetinae | Cytopathogenic Effect, Viral | Endopeptidases | Giant Cells | Humans | Kidney | Membrane Fusion | Mesocricetus | Microscopy, Electron | Molecular Sequence Data | Mutagenesis, Site-Directed | Protein Conformation | Protein Precursors | Recombinant Fusion Proteins | Respiratory Syncytial Viruses | Structure-Activity Relationship | Viral Fusion Proteins | Viral Proteins | Protein Processing, Post-Translational
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