TY - JOUR A1 - Nasiri, Amir Hossein A1 - Wurm, Jan Philip A1 - Immer, Carina A1 - Weickhmann, Anna Katharina A1 - Wöhnert, Jens T1 - An intermolecular G-quadruplex as the basis for GTP recognition in the class V–GTP aptamer T2 - RNA N2 - 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. KW - RNA structure KW - GTP KW - aptamer KW - NMR KW - G-quadruplex KW - ligand binding Y1 - 2017 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42512 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-425126 SN - 1355-8382 SN - 1469-9001 N1 - © 2016 Nasiri et al. This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a CreativeCommons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. VL - 22 IS - 11 SP - 1750 EP - 1759 PB - Laboratory Press ; HighWire Press CY - Cold Spring Harbor, NY ; Stanford, Calif. ER -