Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29877798.
- Also identified by DOI 10.7554/eLife.36381 and PMC identifier 6031431.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Two classes of riboswitches related to the <i>ykkC</i> 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 <i>ykkC</i> RNA motif. These dramatic differences in ligand specificity are achieved with minimal mutations. <i>ykkC</i> aptamers are therefore a prime example of an RNA fold with a rugged fitness landscape. The ease with which the <i>ykkC</i> aptamer acquires new specificity represents a striking case of evolvability in RNA.
Medical subject headings
- Aptamers, Nucleotide
- Nucleic Acid Conformation
- RNA, Bacterial
- Riboswitch