title: Specificity of plasma membrane targeting by the rous sarcoma virus gag protein.
abstract: Budding of C-type retroviruses begins when the viral Gag polyprotein is directed to the plasma membrane by an N-terminal membrane-binding (M) domain. While dispersed basic amino acids within the M domain are critical for stable membrane association and consequent particle assembly, additional residues or motifs may be required for specific plasma membrane targeting and binding. We have identified an assembly-defective Rous sarcoma virus (RSV) Gag mutant that retains significant membrane affinity despite having a deletion of the fourth alpha-helix of the M domain. Examination of the mutant protein's subcellular distribution revealed that it was not localized to the plasma membrane but instead was mistargeted to intracytoplasmic membranes. Specific plasma membrane targeting was restored by the addition of myristate plus a single basic residue, by multiple basic residues, or by the heterologous hydrophobic membrane-binding domain from the cellular Fyn protein. These results suggest that the fourth alpha-helix of the RSV M domain promotes specific targeting of Gag to the plasma membrane, either through a direct interaction with plasma membrane phospholipids or a membrane-associated cellular factor or by maintaining the conformation of Gag to expose specific plasma membrane targeting sequences.
authors.affiliation: Cell and Molecular Biology Program, The Pennsylvania State University College of Medicine, Hershey 17033, USA.
authors.forename: Lisa Z
authors.initials: LZ
authors.lastname: Scheifele
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rhoads
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Parent
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000737:chemistry*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D015683:Gene Products, gag / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D021381:Protein Transport
chemical_list: D015683:Gene Products, gag