NMR structure of the thrombin-binding DNA aptamer stabilized by Sr2+

Area of Science:

• Biochemistry
• Structural Biology
• Nucleic Acid Chemistry

Background:

• Thrombin-binding aptamers (TBA) are short DNA sequences with therapeutic potential.
• G-quadruplex DNA structures are known to bind various metal ions, influencing their stability and function.

Purpose of the Study:

• To elucidate the structural basis of strontium ion (Sr2+) binding to a thrombin-binding DNA aptamer.
• To compare the Sr2+-bound structure with the previously determined potassium ion (K+)-bound structure.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to determine the structure.
• Restrained molecular dynamics simulations were utilized to refine the structural model.

Main Results:

• The Sr2+:TBA complex forms a quadruplex structure with an inter-tetrad distance of 3.8 angstroms, which is 0.7 angstroms larger than in the K+:TBA complex.
• A distinct binding site for Sr2+ was identified, likely involving simultaneous interaction with the oxygen atoms of two G-tetrads in a 1:1 stoichiometry.
• The structural differences highlight the sensitivity of quadruplex DNA to specific metal ion interactions.

Conclusions:

• Quadruplex DNA structures exhibit significant structural plasticity in response to different metal ions.
• Metal ion binding can modulate the biological activity of G-quadruplex DNA structures in vivo, suggesting potential therapeutic implications.