Solution structure of peptides from HIV-1 Vpr protein that cause membrane permeabilization and growth arrest
✍ Scribed by Shenggen Yao; Allan M. Torres; Ahmed A. Azad; Ian G. Macreadie; Raymond S. Norton
- Book ID
- 101284092
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 177 KB
- Volume
- 4
- Category
- Article
- ISSN
- 1075-2617
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✦ Synopsis
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 Vpr 59-86 (residues 59-86 of Vpr) formed an h-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 h-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 Vpr 71-82 and Vpr 71-96 , in which the sequence motifs were located at the N-terminus, were largely unstructured under similar conditions, as judged by their C h H chemical shifts. Thus, the HFRIG and HSRIG motifs adopt h-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.