Tetramolecular DNA quadruplexes in solution: insights into structural diversity and cation movement

Area of Science:

• Structural Biology
• Biochemistry
• Molecular Biophysics

Background:

• Oligonucleotides can form G-quadruplex structures, which are non-canonical DNA secondary structures.
• These structures are of interest for their potential roles in biological processes and as therapeutic targets.

Purpose of the Study:

• To investigate the solution structure of the oligonucleotide d(TG(4)T).
• To characterize the G-quadruplex formation and ion binding properties of d(TG(4)T) and a related U-containing analog.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to determine the three-dimensional structures.
• Ion binding studies were conducted using K(+), Na(+), and (15)NH(4)(+) ions.

Main Results:

• d(TG(4)T) forms a parallel tetramolecular G-quadruplex in solution, existing in equilibrium between two monomeric forms (major and minor).
• The minor form features an additional T-quartet at the 5' end.
• A U-containing analog forms dimeric G-quadruplexes with K(+) and (15)NH(4)(+) but monomers with Na(+).
• (15)NH(4)(+) ion binding sites were identified within the G-quadruplex structures, with cation mobility affected by T-quartets.

Conclusions:

• The study elucidates the complex structural behavior of d(TG(4)T) and its analog, highlighting the influence of sequence and ions on G-quadruplex formation.
• Findings provide insights into cation binding and dynamics within different G-quadruplex architectures.