Riboswitch as a Tandem Riboswitch Regulated by Mn and pH.

Publication Type:

Journal Article

Source:

ACS Chem Biol, Volume 20, Issue 5, p.1010-1019 (2025)

Keywords:

Aptamers, Nucleotide, Crystallography, X-Ray, Escherichia coli, Escherichia coli Proteins, Gene Expression Regulation, Bacterial, Hydrogen-Ion Concentration, Manganese, Models, Molecular, Nucleic Acid Conformation, Riboswitch, RNA, Bacterial, Scattering, Small Angle

Abstract:

<p>The riboswitch regulates and gene expression on the translation level. It contains two tandem domains regulated by Mn and pH. This study investigates the tertiary structure and conformational dynamics of the riboswitch using a combination of crystallography, small-angle X-ray scattering (SAXS), and chemical probing. Our crystal structure of the aptamer domain at 3.8 Å reveals that the riboswitch aptamer domain forms a coaxial superhelix containing three helices connected by a three-way junction (3WJ), with L1 and L3 creating a pocket-like structure that binds Mg and Mn. SHAPE probing and SAXS show that the riboswitch maintains a consistent conformation across pH conditions without Mn but exhibits significant conformational changes under alkaline conditions when Mn is present. These findings align with our proposed model, where Mn binding induces a transition from an &quot;OFF&quot; to an &quot;ON&quot; state in alkaline conditions, while the Mn remains bound to the aptamer independent of pH. This regulatory mechanism allows for more sophisticated control of gene expression, providing a finely tuned adaptive response to environmental changes.</p>

PDB: 
9JGM
Detector: 
PILATUS
Beamline: 
24-ID-C