Reversible Regulation of Protein Binding Affinity by a DNA Machine

Abstract

We report a DNA machine that can reversibly regulate target binding affinity on the basis of distance-dependent bivalent binding. It is a tweezer-like DNA machine that can tune the spatial distance between two ligands to construct or destroy the bivalent binding. The DNA machine can strongly bind to the target protein when the ligands are placed at an appropriate distance but releases the target when the bivalent binding is disrupted by enlargement of the distance between the ligands. This “capture–release” cycle could be repeatedly driven by single-stranded DNA without changing the ligands and target protein