title: Solution structure of peptides from HIV-1 Vpr protein that cause membrane permeabilization and growth arrest.
abstract: Vpr, one of the accessory gene products encoded by HIV-1, is a 96-residue protein with a number of functions, including targeting of the viral pre-integration complex to the nucleus and inducing growth arrest of dividing cells. We have characterized by 2D NMR the solution conformations of bioactive synthetic peptide fragments of Vpr encompassing a pair of H(F/S)RIG sequence motifs (residues 71-75 and 78-82 of HIV-1 Vpr) that cause cell membrane permeabilization and death in yeast and mammalian cells. Due to limited solubility of the peptides in water, their structures were studied in aqueous trifluoroethanol. Peptide Vpr59-86 (residues 59-86 of Vpr) formed an alpha-helix encompassing residues 60-77, with a kink in the vicinity of residue 62. The first of the repeated sequence motifs (HFRIG) participated in the well-defined alpha-helical domain whereas the second (HSRIG) lay outside the helical domain and formed a reverse turn followed by a less ordered region. On the other hand, peptides Vpr71-82 and Vpr71-96, in which the sequence motifs were located at the N-terminus, were largely unstructured under similar conditions, as judged by their C(alpha)H chemical shifts. Thus, the HFRIG and HSRIG motifs adopt alpha-helical and turn structures, respectively, when preceded by a helical structure, but are largely unstructured in isolation. The implications of these findings for interpretation of the structure-function relationships of synthetic peptides containing these motifs are discussed.
authors.affiliation: Biomolecular Research Institute, Parkville, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Yao
authors.forename: A M
authors.initials: AM
authors.lastname: Torres
authors.forename: A A
authors.initials: AA
authors.lastname: Azad
authors.forename: I G
authors.initials: IG
authors.lastname: Macreadie
authors.forename: R S
authors.initials: RS
authors.lastname: Norton
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability; D016336:Gene Products, vpr / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D016336:Gene Products, vpr; D010446:Peptide Fragments