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).