title: Functional analysis of the N-terminal domain of Tat protein of the human immunodeficiency virus type 1.
abstract: The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent trans-activator of the viral long terminal repeat (LTR). The N-terminal region of Tat is rich in proline and acidic residues analogous to the activation domains of other transcription factors such as GAL-4 and CTF/NF-1. Several basic residues are also present in this region. To investigate the role of these structural features in the Tat-mediated trans-activation, we have chemically synthesized and evaluated Tat analogs with alanine or glutamine replacing one or more of these amino acid residues. Our data show that substitution of Glu-2, His-13, or all the proline in the Pro-Xaa3-Pro triad drastically reduced activity. In contrast, changes at Arg-7, Lys-12 and any one proline residue in the triad moderately reduced, and substitution of Lys-19 showed little effect on, activity. These results show that the native structure of the N-terminal 19 amino acid sequence is essential for Tat function, and that the overall topology of this domain and not the acidic residues alone appears necessary for trans-activation.
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania 19104.
authors.forename: M V
authors.initials: MV
authors.lastname: Reddy
authors.forename: M
authors.initials: M
authors.lastname: Desai
authors.forename: J
authors.initials: J
authors.lastname: Jeyapaul
authors.forename: D D
authors.initials: DD
authors.lastname: Prasad
authors.forename: T
authors.initials: T
authors.lastname: Seshamma
authors.forename: D
authors.initials: D
authors.lastname: Palmeri
authors.forename: S A
authors.initials: SA
authors.lastname: Khan
mesh_terms: D000595:Amino Acid Sequence; D015696:Gene Products, tat / Q000737:chemistry / Q000502:physiology*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus