Figure 4.

Mechanisms of ssDNA scanning by facilitated diffusion. (A) Electrostatic interactions between APOBECs and the negatively charged region (blue shaded region) of ssDNA are essential for facilitated diffusion. (B) One-dimensional sliding of the enzyme enables short-range localized searching (≤20 nt). (C) Three-dimensional scanning of the enzyme by jumping enables larger translocations through micro-dissociations and reassociations on ssDNA without diffusion into the bulk solution, but lacks a local search process. (D) Three-dimensional scanning by intersegmental transfer enables even larger translocations mediated through a doubly bound state. Enzymes with two binding domains can simultaneously bind two different regions of ssDNA before dissociating from one region to move onto the other.