Abstract:

<p>Two classes of riboswitches related to the guanidine-I riboswitch bind phosphoribosyl pyrophosphate (PRPP) and guanosine tetraphosphate (ppGpp). Here we report the co-crystal structure of the PRPP aptamer and its ligand. We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with a dramatic 40,000-fold switch in specificity. The ends of the aptamer form a helix that is not present in the guanidine aptamer and is involved in the expression platform. In the mutant, the base of ppGpp replaces G96 in three-dimensional space. This disrupts the S-turn, which is a primary structural feature of the RNA motif. These dramatic differences in ligand specificity are achieved with minimal mutations. aptamers are therefore a prime example of an RNA fold with a rugged fitness landscape. The ease with which the aptamer acquires new specificity represents a striking case of evolvability in RNA.</p>