Fluoride ion encapsulation by Mg2+ ions and phosphates in a fluoride riboswitch.
Significant advances in our understanding of RNA architecture, folding and recognition have emerged from structure-function studies on riboswitches, non-coding RNAs whose sensing domains bind small ligands and whose adjacent expression platforms contain RNA elements involved in the control of gene regulation. We now report on the ligand-bound structure of the Thermotoga petrophila fluoride riboswitch, which adopts a higher-order RNA architecture stabilized by pseudoknot and long-range reversed Watson-Crick and Hoogsteen A•U pair formation. The bound fluoride ion is encapsulated within the junctional architecture, anchored in place through direct coordination to three Mg(2+) ions, which in turn are octahedrally coordinated to water molecules and five inwardly pointing backbone phosphates. Our structure of the fluoride riboswitch in the bound state shows how RNA can form a binding pocket selective for fluoride, while discriminating against larger halide ions. The T. petrophila fluoride riboswitch probably functions in gene regulation through a transcription termination mechanism.
Structural Biology Program, Memorial Sloan-Kettering Center, New York, New York 10065, USA.
Aiming
A
Ren
Kanagalaghatta R
KR
Rajashankar
Dinshaw J
DJ
Patel
D001483:Base Sequence; D001665:Binding Sites; D002413:Cations, Divalent / Q000737:chemistry*; D005459:Fluorides / Q000737:chemistry* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D016965:Gram-Negative Anaerobic Straight, Curved, and Helical Rods / Q000235:genetics*; D008024:Ligands; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D010710:Phosphates / Q000737:chemistry* / Q000378:metabolism; D058928:Riboswitch / Q000235:genetics*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry / Q000378:metabolism
D002413:Cations, Divalent; D008024:Ligands; D010710:Phosphates; D058928:Riboswitch; D014867:Water; D008274:Magnesium; D005459:Fluorides