Protein-DNA recognition mechanisms and specificity

Abstract

The accumulated knowledge about the structure of protein-DNA complexes allowed us to understand the mechanisms of protein-DNA recognition and searching for a specific site on DNA. Obviously, the mechanism of specific DNA recognition by a protein must satisfy two requirements. First, the probability of incorrect binding should be very small. Second, the time to find the "correct" binding site should not be too long. If we assume that protein recognition of a precise site on DNA occurs at some distance from DNA and calculate global minima, we can avoid local minima at short distances. The only long-range interaction is the interaction of charges. The location of charges on DNA in three-dimensional space depends on the local conformation of DNA and thus reflects the DNA sequence and sets the spatial pattern for recognition. Various factors such as counter ion concentration, ionic strength, and pH can affect protein recognition of DNA. Nowadays, the theory of long-range interactions makes it possible to calculate the best mutual spatial arrangement of protein and DNA molecules by charged groups and avoid misplaced binding.

Keywords: Electrostatic potential; Long-range interactions; Protein sliding on DNA; Protein-DNA recognition; Specific site.

Fig. 1

Interaction energy of bicoid protein (1zq3) and DNA (5′-TGCTGTCGACTCCTGACACCAACGTAATCCCCCCATAGAA-3′) with different distances between protein and DNA, from 4 to 60 Å with an increment 4.0 Å. Obtained by Formula (1). The nucleotide sequence of DNA is plotted on the X-axis; the energy of interaction in conventional units is plotted on the Y-axis. Figure taken from the report on RFBR grant 15–04-99605, 2017, with permission of the authors. The true site is shown in bold. Deeper lines correspond to shorter distances