Document 0046
 DOCN  M9580046
 TI    Mutagenesis of the putative alpha-helical domain of the Vpr protein of
       human immunodeficiency virus type 1: effect on stability and virion
       incorporation.
 DT    9506
 AU    Mahalingam S; Khan SA; Murali R; Jabbar MA; Monken CE; Collman RG;
       Srinivasan A; Institute of Biotechnology and Advanced Molecular
       Medicine,; Jefferson Cancer Institute, Thomas Jefferson University,;
       Philadelphia, PA 19107, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3794-8. Unique Identifier :
       AIDSLINE MED/95249560
 AB    vpr is one of the auxiliary genes of human immunodeficiency virus type 1
       (HIV-1) and is conserved in the related HIV-2/simian immunodeficiency
       virus lentiviruses. The unique feature of Vpr is that it is the only
       nonstructural protein incorporated into the virus particle. Secondary
       structural analysis predicted an amphipathic alpha-helical domain in the
       amino terminus of Vpr (residues 17-34) which contains five acidic and
       four leucine residues. To evaluate the role of specific residues of the
       helical domain for virion incorporation, mutagenesis of this domain was
       carried out. Substitution of proline for any of the individual acidic
       residues (Asp-17 and Glu-21, -24, -25, and -29) eliminated the virion
       incorporation of Vpr and also altered the stability of Vpr in cells.
       Conservative replacement of glutamic residues of the helical domain with
       aspartic residues resulted in Vpr characteristic of wild type both in
       stability and virion incorporation, as did substitution of glutamine for
       the acidic residues. In contrast, replacement of leucine residues of the
       helical domain (residues 20, 22, 23, and 26) by alanine eliminated
       virion incorporation function of Vpr. These data indicate that acidic
       and hydrophobic residues and the helical structure in this region are
       critical for the stability of Vpr and its efficient incorporation into
       virus-like particles.
 DE    Amino Acid Sequence  Aspartic Acid  Comparative Study  Drug Stability
       Gene Products, vpr/*CHEMISTRY/*METABOLISM  Genes, vpr  Glutamic Acid
       Hela Cells  Human  HIV-1/*METABOLISM  Molecular Sequence Data
       Mutagenesis, Site-Directed  *Protein Structure, Secondary  Recombinant
       Proteins/CHEMISTRY/METABOLISM  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Transfection  Virion/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).