title: Receptor-triggered membrane association of a model retroviral glycoprotein.
abstract: Current models of retroviral entry hypothesize that interactions between the viral envelope protein and the host receptor(s) induce conformational changes in the envelope protein that activate the envelope protein and initiate fusion. We employed a liposome-binding assay to demonstrate directly and characterize the activation of a model retroviral envelope protein (EnvA) from Rous sarcoma virus (RSV). In the presence of purified viral receptor, the trimeric ectodomain of EnvA was converted from a water-soluble form to a membrane-associated form, consistent with conversion of the envelope protein to its fusogenic state. This activation was nonlinear with respect to receptor concentration, suggesting cooperativity within the trimeric envelope protein. The activated EnvA was stably associated with the target membrane through hydrophobic interactions, behaving like an intrinsic membrane protein. The ability of EnvA to associate with membrane was coincident with a loss of receptor-binding activity, suggesting that during viral entry activated EnvA dissociates from the receptor to facilitate membrane fusion. These results provide direct evidence that receptor binding triggers conversion of the EnvA protein to a membrane-binding form, illustrating that RSV is a useful model for the study of retroviral entry and activation of pH-independent fusion proteins.
authors.affiliation: Department of Microbiology, Graduate Program in Cellular and Molecular Biology, University of Pennsylvania, School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Damico
authors.forename: J
authors.initials: J
authors.lastname: Crane
authors.forename: P
authors.initials: P
authors.lastname: Bates
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000502:physiology*; D002462:Cell Membrane / Q000821:virology; D002784:Cholesterol; D008081:Liposomes; D008561:Membrane Fusion; D051379:Mice; D008954:Models, Biological; D008961:Models, Structural; D010713:Phosphatidylcholines; D011991:Receptors, Virus / Q000502:physiology*; D012190:Retroviridae / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000502:physiology*
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D002784:Cholesterol