Specific minor groove solvation is a crucial determinant of DNA binding site recognition

Abstract

The DNA sequence preferences of nearly all sequence specific DNA binding proteins are influenced by the identities of bases that are not directly contacted by protein. Discrimination between non-contacted base sequences is commonly based on the differential abilities of DNA sequences to allow narrowing of the DNA minor groove. However, the factors that govern the propensity of minor groove narrowing are not completely understood. Here we show that the differential abilities of various DNA sequences to support formation of a highly ordered and stable minor groove solvation network are a key determinant of non-contacted base recognition by a sequence-specific binding protein. In addition, disrupting the solvent network in the non-contacted region of the binding site alters the protein's ability to recognize contacted base sequences at positions 5–6 bases away. This observation suggests that DNA solvent interactions link contacted and non-contacted base recognition by the protein.

Differential Deformability of the DNA Minor Groove and Altered BI/BII Backbone Conformational Equilibrium by the Monovalent Ions Li+, Na+, K+, and Rb+ via Water-Mediated Hydrogen Bonding

“…45 In a recent experimental study it was demonstrated that disruption of the specific solvation pattern in the minor groove dramatically affects a “direct” readout in remote (5-6 bases away) segments of DNA (e.g. in the major groove), 4 a result consistent with the more general observation that the minor groove dimensions (but not those of the major groove) are highly variable in protein-DNA complexes. 1,27 Because other experimental and computational studies indicate the presence of various ions inside the minor groove, 12,14,15,19,21 it is important to provide microscopic insights into the relationship between variations in the minor groove dimensions and changes in the ionic buffer content.…”

How B-DNA Dynamics Decipher Sequence-Selective Protein Recognition

“…3 Protein-DNA shape recognition involves the formation of specific binding sites for positively charged amino-acids, ARG/LYS, indirect contacts with phosphates some direct hydrogen bonds established with DNA bases and interactions mediated through water molecules, depending on the different solvation, above all upon binding the release of water molecules from the protein-DNA interface providing a favorable entropic contribution and it is important for selectivity [2][3][4] Very often, protein binding leads to a conformational change in DNA, and again two different models can be proposed to explain the connection between structural flexibility and binding:…”

DNA triplex structure, thermodynamics, and destabilisation: insight from molecular simulations

“…15,16,52 On the other hand, computational studies of the netropsin-duplex complex in solution have shown that the binding of netropsin decreases the minor-groove width by 1-2 Å, particularly over the base pairs where the charged groups of netropsin are found. 17 The solvent environment has previously been shown to influence the minor groove width 36,53 and, accordingly, it is possible that the solidstate structure measured in crystallographic studies differs from the arguably more biologically relevant aqueous structure studied by simulation. It should be noted that the aforementioned studies focused on the structure of the netropsin-duplex complex, while the structure of the netropsin-triplex complex has not previously been examined.…”