Base flexibility in HIV-2 TAR RNA mapped by solution (15)N, (13)C NMR relaxation

Abstract

Binding of the HIV tat protein to the TAR (transactivating response region) RNA element activates transcription of the HIV viral genome. The complex of TAR with argininamide serves as a model for the RNA conformation in the tat-TAR complex. The dynamics of the HIV-2 TAR-argininamide complex was investigated by measurements of the relaxation rates of protonated base carbon and nitrogen nuclei. Six auto-correlation rates as well as cross-correlation rates were measured to map the frequencies of base motion in the HIV-2 TAR-argininamide complex. These measurements reveal a broad range of dynamic heterogeneity exhibited by hexanucleotide loop, the dinucleotide bulge, and the A-form helical regions. U23 in the bulge undergoes the largest dynamic change on binding argininamide, while U25 remains flexible, reflecting the large conformational change that is triggered upon ligand binding.