       Document 0722
 DOCN  M95A0722
 TI    Role of the conserved dipeptide Gly75 and Cys76 on HIV-1 Vpr function.
 DT    9510
 AU    Mahalingam S; Collman RG; Patel M; Monken CE; Srinivasan A; Institute of
       Biotechnology, Jefferson Cancer Institute, Thomas; Jefferson University,
       Philadelphia, Pennsylvania 19107, USA.
 SO    Virology. 1995 Jul 10;210(2):495-500. Unique Identifier : AIDSLINE
       MED/95343564
 AB    Vpr is one of the accessory proteins encoded by the HIV-1 genome.
       Several interesting features associated with Vpr include incorporation
       into virus particles, ability to oligomerize, localization in the
       nucleus, and positive effect on virus production and replication. In
       order to understand the structure-function relationship of Vpr, we have
       analyzed the role of the Gly75 and Cys76 (GC) residues which are highly
       conserved in HIV-1 Vpr and in Vpr and Vpx of HIV-2/SIV. We have
       generated several substitution mutants involving this dipeptide and have
       evaluated for expression, stability, nuclear localization, and virion
       incorporation of Vpr. Our data demonstrate that the GC residues are not
       essential for virion incorporation and nuclear localization of Vpr.
       Serine substitution for Cys, however, restricted the localization of Vpr
       in the cytoplasm without affecting the Gag-directed incorporation of Vpr
       into virus-like particles. Interestingly, the cysteine-substituted
       mutants showed altered stability in comparison to the wild type, and
       substitution mutants for glycine showed minimal effect on stability.
       These results indicate that the glycine and cysteine do not play a role
       in nuclear localization or virion incorporation properties of Vpr and
       further suggest that these two functions of Vpr may not be
       interdependent.
 DE    Amino Acid Sequence  Cell Nucleus/CHEMISTRY  Conserved
       Sequence/*GENETICS  Cysteine/PHYSIOLOGY  Cytoplasm/CHEMISTRY
       Dipeptides/GENETICS/*PHYSIOLOGY  Gene Products,
       vpr/ANALYSIS/GENETICS/*PHYSIOLOGY  Genes, vpr/GENETICS  Genetic
       Vectors/GENETICS  Glycine/PHYSIOLOGY  Hela Cells  Human
       HIV-1/GENETICS/*PHYSIOLOGY  Mutation/PHYSIOLOGY  RNA
       Polymerases/GENETICS  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  Vaccinia Virus/GENETICS  Virion  Virus Replication/*GENETICS
       JOURNAL ARTICLE

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

