Characterization of the solution conformations of unbound and Tat peptide-bound forms of HIV-1 TAR RNA

Basic peptides from the carboxy terminus of the HIV-I Tat protein bind to t he apical stem-loop region of TAR RNA with high affinity and moderate speci ficity. The conformations of the unbound and 24 residue Tat peptide (Tfr24) -bound forms of TAR RNA have been characterized by NMR spectroscopy. The un bound form of TAR exists in major and minor forms having different trinucle otide bulge conformations. A specific TAR RNA conformational change is obse rved upon complex formation with Tfr24, consisting of coaxial stacking of h elical stems and base triple formation. A U23-A27-U38 base triple is propos ed based on exchangeable proton NMR data, where U23 forms a base pair with A27 in the major groove. No evidence for base triple formation was found fo r Tat peptides in which lysine residues are extensively substituted for arg inine.