Journal
CHEMISTRY & BIOLOGY
Volume 15, Issue 10, Pages 1125-1137Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2008.09.004
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Funding
- Damon Runyon Cancer Research Foundation [DRG-1844-04]
- W.M. Keck Foundation
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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 (K-d similar to 0.8 nM). It is one of few aptamers known to be capable of modulating gene expression in vivo. The 2.2 angstrom 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.
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