Structural and functional properties of an unusual internal fusion peptide in a nonenveloped virus membrane fusion protein.
The avian and Nelson Bay reoviruses are two of only a limited number of nonenveloped viruses capable of inducing cell-cell membrane fusion. These viruses encode the smallest known membrane fusion proteins (p10). We now show that a region of moderate hydrophobicity we call the hydrophobic patch (HP), present in the small N-terminal ectodomain of p10, shares the following characteristics with the fusion peptides of enveloped virus fusion proteins: (i) an abundance of glycine and alanine residues, (ii) a potential amphipathic secondary structure, (iii) membrane-seeking characteristics that correspond to the degree of hydrophobicity, and (iv) the ability to induce lipid mixing in a liposome fusion assay. The p10 HP is therefore predicted to provide a function in the mechanism of membrane fusion similar to those of the fusion peptides of enveloped virus fusion peptides, namely, association with and destabilization of opposing lipid bilayers. Mutational and biophysical analysis suggested that the internal fusion peptide of p10 lacks alpha-helical content and exists as a disulfide-stabilized loop structure. Similar kinked structures have been reported in the fusion peptides of several enveloped virus fusion proteins. The preservation of a predicted loop structure in the fusion peptide of this unusual nonenveloped virus membrane fusion protein supports an imperative role for a kinked fusion peptide motif in biological membrane fusion.
Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
Maya
M
Shmulevitz
Raquel F
RF
Epand
Richard M
RM
Epand
Roy
R
Duncan
D000595:Amino Acid Sequence; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009154:Mutation; D018165:Orthoreovirus / Q000502:physiology*; D030101:Orthoreovirus, Avian / Q000502:physiology*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011784:Quail; D013329:Structure-Activity Relationship; D014162:Transfection; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D008081:Liposomes; D010455:Peptides; D014760:Viral Fusion Proteins