The structural basis for recognition of the PreQ0 metabolite by an unusually small riboswitch aptamer domain

J Biol Chem. 2009 Apr 24;284(17):11012-6. doi: 10.1074/jbc.C900024200. Epub 2009 Mar 4.

Abstract

Riboswitches are RNA elements that control gene expression through metabolite binding. The preQ(1) riboswitch exhibits the smallest known ligand-binding domain and is of interest for its economical organization and high affinity interactions with guanine-derived metabolites required to confer tRNA wobbling. Here we present the crystal structure of a preQ(1) aptamer domain in complex with its precursor metabolite preQ(0). The structure is highly compact with a core that features a stem capped by a well organized decaloop. The metabolite is recognized within a deep pocket via Watson-Crick pairing with C15. Additional hydrogen bonds are made to invariant bases U6 and A29. The ligand-bound state confers continuous helical stacking throughout the core fold, thus providing a platform to promote Watson-Crick base pairing between C9 of the decaloop and the first base of the ribosome-binding site, G33. The structure offers insight into the mode of ribosome-binding site sequestration by a minimal RNA fold stabilized by metabolite binding and has implications for understanding the molecular basis by which bacterial genes are regulated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • Bacillus subtilis / metabolism
  • Base Pairing
  • Binding Sites
  • Crystallography, X-Ray / methods
  • Electrons
  • Hydrogen Bonding
  • Ligands
  • Models, Chemical
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Conformation
  • Protein Structure, Tertiary
  • Pyrimidinones / chemistry*
  • Pyrroles / chemistry*
  • Thermoanaerobacter / metabolism

Substances

  • 7-(aminomethyl)-7-deazaguanine
  • Aptamers, Nucleotide
  • Ligands
  • Pyrimidinones
  • Pyrroles

Associated data

  • PDB/3GCA