Solution structure of peptides from HIV-1 Vpr protein that cause membrane permeabilization and growth arrest.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Solution structure of peptides from HIV-1 Vpr protein that cause membrane permeabilization and growth arrest.

J Pept Sci. 1998 Nov;4(7):426-35. Unique Identifier : AIDSLINE MED/99066695
Yao S; Torres AM; Azad AA; Macreadie IG; Norton RS; Biomolecular Research Institute, Parkville, Victoria, Australia.

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.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Cell Membrane Permeability Gene Products, vpr/*CHEMISTRY Models, Molecular Molecular Sequence Data Nuclear Magnetic Resonance Peptide Fragments/*CHEMISTRY Protein Conformation
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