title: An intermolecular G-quadruplex as the basis for GTP recognition in the class V-GTP aptamer.
abstract: Many naturally occurring or artificially created RNAs are capable of binding to guanine or guanine derivatives with high affinity and selectivity. They bind their ligands using very different recognition modes involving a diverse set of hydrogen bonding and stacking interactions. Apparently, the potential structural diversity for guanine, guanosine, and guanine nucleotide binding motifs is far from being fully explored. Szostak and coworkers have derived a large set of different GTP-binding aptamer families differing widely in sequence, secondary structure, and ligand specificity. The so-called class V-GTP aptamer from this set binds GTP with very high affinity and has a complex secondary structure. Here we use solution NMR spectroscopy to demonstrate that the class V aptamer binds GTP through the formation of an intermolecular two-layered G-quadruplex structure that directly incorporates the ligand and folds only upon ligand addition. Ligand binding and G-quadruplex formation depend strongly on the identity of monovalent cations present with a clear preference for potassium ions. GTP binding through direct insertion into an intermolecular G-quadruplex is a previously unobserved structural variation for ligand-binding RNA motifs and rationalizes the previously observed specificity pattern of the class V aptamer for GTP analogs.
authors.affiliation: Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Johann-Wolfgang-Goethe-University Frankfurt, 60438 Frankfurt, Germany.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Nasiri
authors.affiliation: Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Johann-Wolfgang-Goethe-University Frankfurt, 60438 Frankfurt, Germany.
authors.forename: Jan Philip
authors.initials: JP
authors.lastname: Wurm
authors.affiliation: Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Johann-Wolfgang-Goethe-University Frankfurt, 60438 Frankfurt, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Immer
authors.affiliation: Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Johann-Wolfgang-Goethe-University Frankfurt, 60438 Frankfurt, Germany.
authors.forename: Anna Katharina
authors.initials: AK
authors.lastname: Weickhmann
authors.affiliation: Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Johann-Wolfgang-Goethe-University Frankfurt, 60438 Frankfurt, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wöhnert
mesh_terms: D052157:Aptamers, Nucleotide / Q000378:metabolism*; D001665:Binding Sites; D002414:Cations, Monovalent; D054856:G-Quadruplexes; D006160:Guanosine Triphosphate / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D052157:Aptamers, Nucleotide; D002414:Cations, Monovalent; D006160:Guanosine Triphosphate
keywords: G-quadruplex; GTP; NMR; RNA structure; aptamer; ligand binding