DNA conformations and their sequence preferences

Abstract

The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA. Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering. Besides the known variants of the A-, B- and Z-DNA forms, we have also identified combined A + B backbone-deformed conformers, e.g. with alpha/gamma switches, and a few conformers with a syn orientation of bases occurring e.g. in G-quadruplex structures. A plethora of A- and B-like conformers show a close relationship between the A- and B-form double helices. A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the A- and B- forms. Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests. The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail.

Figure 1.

The analyzed unit is defined by ten torsion angles from γ to δ + 1 along the backbone plus torsions χ and χ + 1 at the glycosidic bond. B0 and B1 symbolize the bases.

Figure 2.

Two-dimensional scattergrams of torsion angles in naked DNA (Dataset 2 from Table 1, dark blue) and in DNA from complexes (Dataset 1, cyan). A, B and Z are the respective double-helical forms, r stands for purines and y for pyrimidines. The conformations of almost 4000 RNA dinucleotides are plotted as pink dots for comparison.

Figure 3.

Dinucleotide conformations in the crystal structure of the histone-core particle 1KX5 (89). Dinucleotides are classified into four conformational families and labeled as follows: BI–1, BII–2, BI conformers with a α + 1/γ + 1 switch (Clusters 113–117) – 3, unclassifiable conformers – 4. One DNA chain, labeled I in the PDB file and drawn in blue and marked in the left y axis in the Figure, is traced from the 5′-end to the 3′-end. The other chain, labeled J in the PDB file and drawn in red in the right y axis, is traced from the 3′-end to the 5′-end. Base paired nucleotides from chains I and J have therefore the same x coordinate.