The structural basis for recognition of the PreQ0 metabolite by an unusually small riboswitch aptamer domain.
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.
Spitale
Robert C
RC
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Torelli
Andrew T
AT
Krucinska
Jolanta
J
Bandarian
Vahe
V
Wedekind
Joseph E
JE
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
C096876:7-(aminomethyl)-7-deazaguanine; D052157:Aptamers, Nucleotide; D008024:Ligands; D011744:Pyrimidinones; D011758:Pyrroles