Binding of a Telomestatin Derivative Changes the Mechanical Anisotropy of a Human Telomeric G-Quadruplex.

Mechanical anisotropy is an essential property for biomolecules to assume structural and functional roles in mechanobiology. However, there is insufficient information on the mechanical anisotropy of ligand-biomolecule complexes. Herein, we investigated the mechanical property of individual human telomeric G-quadruplexes bound to telomestatin, using optical tweezers. Stacking of the ligand to the G-tetrad planes changes the conformation of the G-quadruplex, which resembles a balloon squeezed in certain directions. Such a squeezed balloon effect strengthens the G-tetrad planes, but dislocates and weakens the loops in the G-quadruplex upon ligand binding. These dynamic interactions indicate that the binding between the ligand and G-quadruplex follows the induced-fit model. We anticipate that the altered mechanical anisotropy of the ligand-G-quadruplex complex can add additional level of regulations on the motor enzymes that process DNA or RNA molecules.