RNA architecture dictates the conformations of a bound peptide

Background: The biological function of several viral and bacteriophage prot eins, and their arginine-rich subdomains, involves RNA-mediated interaction s. It has been shown recently that bound peptides adopt either beta-hairpin or alpha-helical conformations in viral and phage peptide-RNA complexes. W e have compared the structures of the arginine rich peptide domain of HIV-1 Rev bound to two RNA aptamers to determine whether RNA architecture can di ctate the conformations of a bound peptide. Results: The core-binding segment of the HIV-1 Rev peptide class II RNA apt amer complex spans the two-base bulge and hairpin loop of the bound RNA and the carboxy-terminal segment of the bound peptide. The bound peptide is an chored in place by backbone and sidechain intermolecular hydrogen bonding a nd van der Waals stacking interactions. One of the bulge bases participates in U.(A.U) base triple formation, whereas the other is looped out and flap s over the bound peptide in the complex. The seven-residue hairpin loop is closed by a sheared G.A mismatch pair with several pyrimidines looped out o f the hairpin fold. Conclusions: Our structural studies establish that RNA architecture dictate s whether the same HIV-1 Rev peptide folds into an extended or alpha-helica l conformation on complex formation. Arginine-rich peptides can therefore a dapt distinct secondary folds to complement the tertiary folds of their RNA targets. This contrasts with protein-RNA complexes in which elements of RN A secondary structure adapt to fit within the tertiary folds of their prote in targets.