Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations.

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Human telomere (ht) DNA folding into G-quadruplexes and ligand interactions are actively researched.
• The fundamental forces governing these folding and recognition processes remain largely uncharacterized.

Purpose of the Study:

• To elucidate the thermodynamic forces behind the folding of a 22-mer ht-DNA fragment (Tel22) into G-quadruplex structures.
• To characterize the forces involved in the binding of ions (K+, Na+) and bisquinolinium ligands to Tel22 G-quadruplexes.
• To develop a predictive model for Tel22 behavior under varying conditions.

Main Methods:

• Calorimetric and spectroscopic methods were employed to monitor structural changes.
• Gel electrophoresis was used to analyze DNA fragment behavior.
• Global model analysis integrated diverse experimental data for comprehensive characterization.

Main Results:

• The thermodynamic forces governing stable Tel22 G-quadruplex formation, folding intermediates, and ligand-quadruplex complexes were characterized.
• A predictive model was established for Tel22 behavior based on temperature, salt, and ligand concentrations.
• Insights into the heterogeneity of ht-DNA folding and binding pathways were gained.

Conclusions:

• This research provides a thermodynamic framework for understanding ht-DNA G-quadruplex formation and ligand interactions.
• The findings contribute to a better comprehension of ht-DNA structural polymorphism and folding heterogeneity.
• This work facilitates the prediction of Tel22 behavior in various aqueous solution conditions.