Structural basis for specific, high-affinity tetracycline binding by an in vitro evolved aptamer and artificial riboswitch.

Publication Type:

Journal Article


Chemistry & biology, Volume 15, Issue 10, p.1125-37 (2008)


2008, Aptamers, Nucleotide, Base Sequence, Basic Sciences Division, Binding Sites, Center-Authored Paper, Crystallography, X-Ray, Genomics Core Facility, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Proteomics Core Facility, Scientific Imaging Core Facility, Shared Resources, Substrate Specificity, Tetracycline, Water


The tetracycline aptamer is an in vitro selected RNA that binds to the antibiotic with the highest known affinity of an artificial RNA for a small molecule (Kd approximately 0.8 nM). It is one of few aptamers known to be capable of modulating gene expression in vivo. The 2.2 A resolution cocrystal structure of the aptamer reveals a pseudoknot-like fold formed by tertiary interactions between an 11 nucleotide loop and the minor groove of an irregular helix. Tetracycline binds within this interface as a magnesium ion chelate. The structure, together with previous biochemical and biophysical data, indicates that the aptamer undergoes localized folding concomitant with tetracycline binding. The three-helix junction, h-shaped architecture of this artificial RNA is more complex than those of most aptamers and is reminiscent of the structures of some natural riboswitches.