Human immunodeficiency virus type 2 (HIV-2) trans-activator (Tat): functional domains and the search for trans-dominant negative mutants.
Human immunodeficiency virus type 2 (HIV-2) trans-activator (Tat) is an important trans-regulator of viral gene expression. It differs from the related HIV-1 Tat in certain aspects of its structure and function. HIV-2 Tat is composed of 130 amino acids versus 86 amino acids for HIV-1 Tat. Apart from certain conserved regions, there is little homology between the two Tats. They also differ in their ability to trans-activate HIV-2 and HIV-1 long terminal repeat (LTR)-directed gene expression. As an aid to understanding its mechanism of action, the functional domains important for HIV-2 Tat trans-activation of HIV-2 and HIV-1 LTR-directed gene expression were investigated. Like HIV-1 Tat, HIV-2 Tat contains conserved cysteine- and arginine-rich domains important for its function. However, HIV-2 Tat differs from HIV-1 Tat in that about 20% of the HIV-2 Tat at the amino terminus was not essential for its trans-activation function while HIV-1 Tat amino terminus is reportedly a part of its activation domain. Similarly, about 30% of the protein at the carboxy terminus of HIV-2 Tat was not essential. A domain critical for HIV-2 Tat-mediated trans-activation was located just upstream of the cysteine-rich domain. This segment is predicted to adopt an alpha-helical conformation and also contains acidic amino acid residues; thus, it may resemble amphipathic helix-type activation domains found in some transcriptional factors. A region with predicted hydrophobic alpha-helical character located between the cysteine- and arginine-rich domains was also important for HIV-2 Tat function. HIV-2 Tat mutants that were analogs of HIV-1 Tat trans-dominant negative mutants did not display such a phenotype.
Arya
S K
SK
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
D000595:Amino Acid Sequence; D016384:Consensus Sequence; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics; D015498:HIV-2 / Q000235:genetics*; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000382:microbiology; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D012333:RNA, Messenger; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus