Tat is an essential protein of the human immunodeficiency virus type 1 (HIV-1). It activates transcription by specifically binding a stem-loop element in the viral long terminal repeat through its highly basic arginine-rich domain. Conserved lysine residues at positions 50 and 51 inside this domain have been recently reported to be the targets of post-translational modification by acetylation, and mutation of these residues has pointed out its relevance to protein function. In an attempt to shed light on the molecular basis of the functional differences found for Tat mutants we have performed a series of molecular dynamics simulations on wt Tat, Lys50/51 --> Arg50/51, Lys50/51 --> Ala50/51 and acetylated Lys50 from HIV-1 strain Z2. Theoretical results are compared with a homogeneous set of in vivo transactivation assays on the corresponding Tat mutants from the strain B2, which exhibits high structural similarity with Tat from HIV-1 strain Z2. Remarkable correlation is found between the degree of structure conservation and the transactivation capabilities of Tat mutants.
