The importance of helix P1 stability for structural pre-organization and ligand binding affinity of the adenine riboswitch aptamer domain

RNA Biol. 2014;11(5):655-6. doi: 10.4161/rna.29439. Epub 2014 Jun 12.

Abstract

We report here an in-depth characterization of the aptamer domain of the transcriptional adenine-sensing riboswitch (pbuE) by NMR and fluorescence spectroscopy. By NMR studies, the structure of two aptamer sequences with different lengths of the helix P1, the central element involved in riboswitch conformational switching, was characterized. Hydrogen-bond interactions could be mapped at nucleotide resolution providing information about secondary and tertiary structure, structure homogeneity and dynamics. Our study reveals that the elongation of helix P1 has pronounced effects not only on the local but on the global structure of the apo aptamer domain. The structural differences induced by stabilizing helix P1 were found to be linked to changes of the ligand binding affinity as revealed from analysis of kinetic and thermodynamic data obtained from stopped-flow fluorescence studies. The results provide new insight into the sequence-dependent fine tuning of the structure and function of purine-sensing riboswitches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / metabolism*
  • Aptamers, Nucleotide / metabolism*
  • Base Pairing
  • Ligands
  • Magnesium / metabolism
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation
  • RNA Stability
  • RNA, Bacterial / chemistry*
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism*
  • Riboswitch*
  • Thermodynamics

Substances

  • Aptamers, Nucleotide
  • Ligands
  • RNA, Bacterial
  • Riboswitch
  • Magnesium
  • Adenine