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

ABSTRACT: 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.

SUBMITTER: Xiao H

PROVIDER: S-EPMC2626642 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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

Xiao Hong H Edwards Thomas E TE Ferré-D'Amaré Adrian R AR

Chemistry & biology 20081001 10

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 interfac ...[more]

PMID: 18940672

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