Characterization of a leucine-zipper-like domain in Vpr protein of human immunodeficiency virus type 1.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Characterization of a leucine-zipper-like domain in Vpr protein of human immunodeficiency virus type 1.

Gene. 1996 Oct 31;178(1-2):7-13. Unique Identifier : AIDSLINE MED/97080539
Wang L; Mukherjee S; Narayan O; Zhao LJ; Marion Merrell Dow Foundation, Department of Microbiology,; Molecular Genetics and Immunology, University of Kansas Medical; Center, Kansas City 66160-7424, USA.

Abstract: Human immunodeficiency virus type 1 (HIV-1) replicates productively in vitro in CD4(+)-T cells and/or macrophages. In the host, however, HIV-1 replication may be restricted by the quiescence of susceptible cells. Vpr is a 15-kDa late viral gene product, which is assembled in the virion and suspected to enhance HIV-1 replication in the infected host. We demonstrated previously that Vpr interacted specifically with the cellular transcription factor Sp1, and activated transcription from the HIV-1 long-terminal-repeat. Both Vpr-Sp1 interaction and trans-activation by Vpr required a central Leu/Ile-rich domain (LR domain, aa 60-81) in Vpr. This domain of Vpr was also found critical for Vpr interaction with another cellular protein of 180 kDa. We now provide biochemical evidence that the Vpr LR-domain has a leucine-zipper-like structure. The leucine-zipper structure has been found in a variety of cellular transcription factors, which use the leucine-zipper domain to form a specific dimer before they can bind to DNA through an upstream basic domain. The LR domain of HIV-1 Vpr, when fused to the basic domain of the cellular transcription factor CREB, was capable of supporting specific DNA binding by the CREB basic domain. Point mutational analysis of the Leu/Ile residues in the LR domain suggested that multiple Leu/Ile residues may be involved in maintaining the leucine-zipper-like structure. Mutagenesis in the context of the full-length Vpr also helped identify Leu/Ile residues may be involved in maintaining the leucine-zipper-like structure. Mutagenesis in the context of the full-length Vpr also helped identify Leu/Ile residues critical for Vpr interaction with the cellular 180-kDa protein. These results suggested that the leucine-zipper-like domain may be an important functional determinant for HIV-1 Vpr.

Keywords: Amino Acid Sequence DNA/METABOLISM DNA-Binding Protein, Cyclic AMP-Responsive/GENETICS/METABOLISM Gene Products, vpr/*CHEMISTRY/GENETICS/METABOLISM Human HIV-1/*CHEMISTRY/GENETICS/METABOLISM *Leucine Zippers Molecular Sequence Data Mutagenesis, Site-Directed Point Mutation Protein Binding Protein Conformation Recombinant Fusion Proteins/GENETICS/METABOLISM Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE
970228
M9721886

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