title: Structural Basis for Ligand Binding to the Guanidine-I Riboswitch.
abstract: The guanidine-I riboswitch is a conserved RNA element with approximately 2,000 known examples across four phyla of bacteria. It exists upstream of nitrogen metabolism and multidrug resistance transporter genes and alters expression through the specific recognition of a free guanidinium cation. Here we report the structure of a guanidine riboswitch aptamer from Sulfobacillus acidophilus at 2.7 Å resolution. Helices P1, P1a, P1b, and P2 form a coaxial stack that acts as a scaffold for ligand binding. A previously unidentified P3 helix docks into P1a to form the guanidinium binding pocket, which is completely enclosed. Every functional group of the ligand is recognized through hydrogen bonding to guanine bases and phosphate oxygens. Guanidinium binding is further stabilized through cation-π interactions with guanine bases. This allows the riboswitch to recognize guanidinium while excluding other bacterial metabolites with a guanidino group, including the amino acid arginine.
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06511, USA; Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Reiss
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06511, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06511, USA; Chemical Biology Institute, Yale University, West Haven, CT 06516, USA. Electronic address: scott.strobel@yale.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Strobel
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000378:metabolism; D000068016:Eubacteriales / Q000235:genetics*; D018360:Crystallography, X-Ray; D019791:Guanidine / Q000378:metabolism*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D059370:RNA Folding; D012329:RNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D058928:Riboswitch
chemical_list: D052157:Aptamers, Nucleotide; D008024:Ligands; D012329:RNA, Bacterial; D058928:Riboswitch; D019791:Guanidine
keywords: RNA; X-ray crystallography; bacteria; cation-pi; guanidine; riboswitch; ykkC