title: Unusual topological arrangement of structural motifs in the baboon reovirus fusion-associated small transmembrane protein.
abstract: Select members of the Reoviridae are the only nonenveloped viruses known to induce syncytium formation. The fusogenic orthoreoviruses accomplish cell-cell fusion through a distinct class of membrane fusion-inducing proteins referred to as the fusion-associated small transmembrane (FAST) proteins. The p15 membrane fusion protein of baboon reovirus is unique among the FAST proteins in that it contains two hydrophobic regions (H1 and H2) recognized as potential transmembrane (TM) domains, suggesting a polytopic topology. However, detailed topological analysis of p15 indicated only the H1 domain is membrane spanning. In the absence of an N-terminal signal peptide, the H1 TM domain serves as a reverse signal-anchor to direct p15 membrane insertion and a bitopic N(exoplasmic)/C(cytoplasmic) topology. This topology results in the translocation of the smallest ectodomain ( approximately 20 residues) of any known viral fusion protein, with the majority of p15 positioned on the cytosolic side of the membrane. Mutagenic analysis indicated the unusual presence of an N-terminal myristic acid on the small p15 ectodomain is essential to the fusion process. Furthermore, the only other hydrophobic region (H2) present in p15, aside from the TM domain, is located within the endodomain. Consequently, the p15 ectodomain is devoid of a fusion peptide motif, a hallmark feature of membrane fusion proteins. The exceedingly small, myristoylated ectodomain and the unusual topological distribution of structural motifs in this nonenveloped virus membrane fusion protein necessitate alternate models of protein-mediated membrane fusion.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. roy.duncan@dal.ca
authors.forename: Sandra
authors.initials: S
authors.lastname: Dawe
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Corcoran
authors.forename: Eileen K
authors.initials: EK
authors.lastname: Clancy
authors.forename: Jayme
authors.initials: J
authors.lastname: Salsman
authors.forename: Roy
authors.initials: R
authors.lastname: Duncan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015726:Giant Cells; D008969:Molecular Sequence Data; D019814:Myristic Acid; D018165:Orthoreovirus / Q000502:physiology*; D017434:Protein Structure, Tertiary; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014760:Viral Fusion Proteins; D019814:Myristic Acid