Adenine/adenine contacts defined in the G-quadruplex for highly selective Tb³⁺ binding

Area of Science:

• Biochemistry
• Molecular Biology
• Materials Science

Background:

• Nucleic acid folding is significantly influenced by metal ions, with G-quadruplex (G4) structures typically dependent on K⁺/Na⁺ coordination.
• Developing G4 constructs selective for high-valent metal ions is challenging due to nonspecific phosphate backbone interactions.

Purpose of the Study:

• To investigate a higher-order G4 structure for selective high-valent metal ion binding.
• To explore the potential of G4 DNA as an aptamer-like material for terbium (Tb³⁺) ion detection.

Main Methods:

• Characterization of a higher-order G4 structure (GGA8) from the human c-myb promoter.
• Stoichiometric analysis of Tb³⁺ ion recruitment to the G4 junction.
• Investigation of Tb³⁺ binding sites within the G4 structure using A/A contacts.

Main Results:

• A GGA repeat-derived G4 structure (GGA8) was found to recruit three Tb³⁺ ions specifically at A/A contacts.
• Tb³⁺ binding did not disrupt the overall G4 structure due to its inherent stability in K⁺.
• This specific A/Tb³⁺/A binding motif was also observed in a KRAS promoter G4 structure, indicating broader applicability.

Conclusions:

• The GGA8 G4 structure exhibits high selectivity for Tb³⁺ ions, unaffected by other high-valent metal ions.
• This discovery suggests potential for GGA8 as a Tb³⁺-specific DNA aptamer for ion detection and recovery.
• The findings encourage the search for higher-order G4 structures for selective coordination of high-valent metal ions.