Structure of the Guanidine III Riboswitch

Cell Chem Biol. 2017 Nov 16;24(11):1407-1415.e2. doi: 10.1016/j.chembiol.2017.08.021. Epub 2017 Oct 5.


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: RNA structure; X-ray crystallography; gene regulation; riboregulation.

MeSH terms

  • Actinobacteria / genetics
  • Actinobacteria / metabolism
  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Guanidine / chemistry
  • Guanidine / metabolism
  • Guanine / chemistry
  • Hydrogen Bonding
  • Models, Molecular
  • Nucleic Acid Conformation
  • Riboswitch*


  • Riboswitch
  • Guanine
  • Guanidine