Cell Chemical Biology
Volume 24, Issue 11, 16 November 2017, Pages 1407-1415.e2
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Article
Structure of the Guanidine III Riboswitch

https://doi.org/10.1016/j.chembiol.2017.08.021Get rights and content
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Highlights

  • The guanidine III riboswitch forms a pseudoknot with a triplex section

  • The conserved core forms a left-handed helical ramp that binds a guanidine molecule

  • Guanidine is H-bonded to two guanine bases, a 2′-OH, and makes a π-cation interaction

  • Four modified guanidine compounds also bind to the pocket, which is open on one side

Summary

Riboswitches are structural elements found in mRNA molecules that couple small-molecule binding to regulation of gene expression, usually by controlling transcription or translation. We have determined high-resolution crystal structures of the ykkC guanidine III riboswitch from Thermobifida fusca. The riboswitch forms a classic H-type pseudoknot that includes a triple helix that is continuous with a central core of conserved nucleotides. These form a left-handed helical ramp of inter-nucleotide interactions, generating the guanidinium cation binding site. The ligand is hydrogen bonded to the Hoogsteen edges of two guanine bases. The binding pocket has a side opening that can accommodate a small side chain, shown by structures with bound methylguanidine, aminoguanidine, ethylguanidine, and agmatine. Comparison of the new structure with those of the guanidine I and II riboswitches reveals that evolution generated three different structural solutions for guanidine binding and subsequent gene regulation, although with some common elements.

Keywords

gene regulation
RNA structure
X-ray crystallography
riboregulation

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