Complete Mapping of DNA-Protein Interactions at the Single-Molecule Level.

DNA-protein interaction plays an essential role in the storage, expression, and regulation of genetic information. A 1D/3D facilitated diffusion mechanism has been proposed to explain the extraordinarily rapid rate of DNA-binding protein (DBP) searching for cognate sequence along DNA and further studied by single-molecule experiments. However, direct observation of the detailed chronological protein searching image is still a formidable challenge. Here, for the first time, a single-molecule electrical monitoring technique is utilized to realize label-free detection of the DBP-DNA interaction process based on high-gain silicon nanowire field-effect transistors (SiNW FETs). The whole binding process of WRKY domain and DNA has been visualized with high sensitivity and single-base resolution. Impressively, the swinging of hydrogen bonds between amino acid residues and bases in DNA induce the dynamic collective motion of DBP-DNA. This in situ, label-free electrical detection platform provides a practical experimental methodology for dynamic studies of various biomolecules.