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

Recently various pathways of human telomere (ht) DNA folding into G-quadruplexes and of ligand binding to these structures have been proposed. However, the key issue as to the nature of forces driving the folding and recognition processes remains unanswered. In this study, structural changes of 22-m...

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Bibliographic Details
Published in:Biophysical journal 2015-06, Vol.108 (12), p.2903-2911
Main Authors: Bončina, Matjaž, Hamon, Florian, Islam, Barira, Teulade-Fichou, Marie-Paule, Vesnaver, Gorazd, Haider, Shozeb, Lah, Jurij
Format: Article
Language:English
Subjects:
Aqueous solutions
Binding sites
Deoxyribonucleic acid
DNA
G-Quadruplexes
Humans
Ions
Ligands
Molecular Dynamics Simulation
Polymorphism
Potassium - chemistry
Proteins and Nucleic Acids
Recognition
Sodium - chemistry
Telomere - chemistry
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Summary:Recently various pathways of human telomere (ht) DNA folding into G-quadruplexes and of ligand binding to these structures have been proposed. However, the key issue as to the nature of forces driving the folding and recognition processes remains unanswered. In this study, structural changes of 22-mer ht-DNA fragment (Tel22), induced by binding of ions (K+, Na+) and specific bisquinolinium ligands, were monitored by calorimetric and spectroscopic methods and by gel electrophoresis. Using the global model analysis of a wide variety of experimental data, we were able to characterize the thermodynamic forces that govern the formation of stable Tel22 G-quadruplexes, folding intermediates, and ligand-quadruplex complexes, and then predict Tel22 behavior in aqueous solutions as a function of temperature, salt concentration, and ligand concentration. On the basis of the above, we believe that our work sets the framework for better understanding the heterogeneity of ht-DNA folding and binding pathways, and its structural polymorphism.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2015.05.001