Interplay of ‘induced fit’ and preorganization in the ligand induced folding of the aptamer domain of the guanine binding riboswitch
Riboswitches are highly structured elements in the 50-untranslated regions (50-UTRs) of messenger RNA that control gene expression by specifically binding to small metabolite molecules. They consist of an aptamer domain responsible for ligand binding and an expression platform. Ligand binding in the aptamer domain leads to conformational changes in the expression platform that result in transcription termination or abolish ribosome binding. The guanine riboswitch binds with high-specificity to guanine and hypoxanthine and is among the smallest riboswitches described so far. The X-ray-structure of its aptamer domain in complex with guanine/ hypoxanthine reveals an intricate RNA-fold consisting of a three-helix junction stabilized by longrange base pairing interactions. We analyzed the conformational transitions of the aptamer domain induced by binding of hypoxanthine using highresolution NMR-spectroscopy in solution. We found that the long-range base pairing interactions are already present in the free RNA and preorganize its global fold. The ligand binding core region is lacking hydrogen bonding interactions and therefore likely to be unstructured in the absence of ligand. Mg2+-ions are not essential for ligand binding and do not change the structure of the RNA-ligand complex but stabilize the structure at elevated temperatures. We identified a mutant RNA where the long-range base pairing interactions are disrupted in the free form of the RNA but form upon ligand binding in an Mg2+-dependent fashion. The tertiary interaction motif is stable outside the riboswitch context.
|Author:||Jonas Noeske, Janina Buck, Boris Fürtig, Hamid Reza Nasiri, Harald Schwalbe, Jens Wöhnert|
|Date of Publication (online):||06.08.2007|
|Year of first Publication:||2007|
|Publishing Institution:||Univ.-Bibliothek Frankfurt am Main|
|Source:||Nucleic acids research, 2007, Vol. 35, No. 2, 572–583, doi:10.1093/nar/gkl1094. - http://nar.oxfordjournals.org/cgi/content/full/35/2/572|
|Institutes:||Biochemie und Chemie|
|Dewey Decimal Classification:||570 Biowissenschaften; Biologie|
(c) 2006 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
|Licence (German):||Veröffentlichungsvertrag für Publikationen ohne Print on Demand|