Previous studies have shown that in the absence of ligand, the queC aptamer domain folds into a non-native hairpin, in which the 5 0 -strand frame-shifts to allow the first two guanine residues to base pair, with the 12 nt ssRNA tail lacking any tertiary interactions (26) . The 2D C-H NMR spectra of the 36 nt queC minimal aptamer domain ( Figure 1A ), in the absence of ligand, show severe resonance overlap and large variations in resonance intensities indicating a highly disordered conformation ( Figure 1B ). Excess imino proton resonances as well as 1 H-15 N NOE data indicate that the unbound queC aptamer domain is in equilibrium between native and non-native hairpin conformations (data not shown), consistent with previous NMR studies (26) .