title: The structural basis for recognition of the PreQ0 metabolite by an unusually small riboswitch aptamer domain.
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.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Spitale
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Torelli
authors.forename: Jolanta
authors.initials: J
authors.lastname: Krucinska
authors.forename: Vahe
authors.initials: V
authors.lastname: Bandarian
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Wedekind
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001412:Bacillus subtilis / Q000378:metabolism; D020029:Base Pairing; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods; D004583:Electrons; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011744:Pyrimidinones / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D046968:Thermoanaerobacter / Q000378:metabolism
chemical_list: C096876:7-(aminomethyl)-7-deazaguanine; D052157:Aptamers, Nucleotide; D008024:Ligands; D011744:Pyrimidinones; D011758:Pyrroles