Locating Monovalent Cations in the Grooves of B-DNA^,

Abstract

Here we demonstrate that monovalent cations can localize around B-DNA in geometrically regular, sequence-specific sites in oligonucleotide crystals. Positions of monovalent ions were determined from high-resolution X-ray diffraction of DNA crystals grown in the presence of thallium(I) cations (Tl(+)). Tl(+) has previously been shown to be a useful K(+) mimic. Tl(+) positions determined by refinement of model to data are consistent with positions determined using isomorphous F(Tl) - F(K) difference Fouriers and anomalous difference Fouriers. None of the observed Tl(+) sites surrounding CGCGAATTCGCG are fully occupied by Tl(+) ions. The most highly occupied sites, located within the G-tract major groove, have estimated occupancies ranging from 20% to 35%. The occupancies of the minor groove sites are estimated to be around 10%. The Tl(+) positions in general are not in direct proximity to phosphate groups. The A-tract major groove appears devoid of localized cations. The majority of the observed Tl(+) ions interact with a single duplex and so are not engaged in lattice interactions or crystal packing. The locations of the cation sites are dictated by coordination geometry, electronegative potential, avoidance of electropositive amino groups, and cation-pi interactions. It appears that partially dehydrated monovalent cations, hydrated divalent cations, and polyamines compete for a common binding region on the floor of the G-tract major groove.

Single molecule detection of direct, homologous, DNA/DNA pairing

“…Although extensive further theoretical and experimental work is required before firm conclusions can be formed, one observation presented above helps to discriminate among models proposed thus far: we find that the rate and extent of pairing increases progressively with temperature up to 40°C and then decreases. In general, indirect pairing models depend on the matching of the conformations of two nearby dsDNA molecules, and it has been predicted that conformationbased models [e.g., including sequence-dependent binding of ions (41,42)] should exhibit exactly the pattern of temperature dependence that we observe. At low temperatures, homologous molecules may get frozen in nonmatching conformations that do not result in a strong attraction.…”

A Review of the Role of the Sequence-Dependent Electrostatic Landscape in DNA Alkylation Patterns

“…The self-complementary Drew-Dickerson dodecamer (DDD) (Figure 9), has been crystallized in the presence of Tl + (65). The locations of monovalent and divalent cations are depicted in Figure 7.…”

“…Structures emergent from molecular dynamics calculations in which the amino group was constrained to be proximate to O 6 -position at G 10 , on the floor of the major groove, were consistent with experimental NOE's, and indicated the possibility of axial bending (Figure 12). The interpretation of the data that emerged from electrostatic footprinting (90,91) and NMR (105) studies posited that, as a consequence of favorable electrostatic interactions, the tethered amine occupied conformational space in the vicinity of O 6 and N7 of G 10 , inducing DNA bending, and enabling the release of a diffusible cation(s) from a high-affinity major groove cation binding site associated with the CGCG tracts of the DDD (65). Indeed, as mentioned above, the preferential binding of monovalent cations within the major groove in CGCG has been substantiated by crystallographic analysis in the presence of Tl + (Figure 7) (65).…”

“…This composite shows that G's are high occupancy cation binding sites, even for monovalent cations: blue, near O 6 -G; red, near both O 6 -and N7-G; cyan, near N7-G; yellow, near both bases in dinucleotide step (generally O 6 -and N7-G). Relaxed stereoview of 5′-d(CGCGAATTCGCG) 2 (DDD) and associated Tl + ions based upon 1.2 Å resolution x-ray data (65). Tl + ions are depicted by green spheres; the sole Mg 2+ ion is depicted by a yellow sphere.…”

Curvature and Deformation of Nucleic Acids: Overview

“…Since GC-rich sequences preferentially localize cations in the major groove (111)(112)(113)(114)(115)(116)(117) and undergo the B-to Α-form structural transition relatively easily (118)(119)(120)(121)(122), and Α-tract DNAs preferentially bind cations in the minor groove (57,58,107,109,(123)(124)(125) and have the relatively rigid B'-DNA structure (40, 41), Hud and coworkers (110) have proposed that DNA conformation is determined by the relative proportion of counterions preferentially localized in the major and minor grooves of GC-rich and Α-tract sequences, respectively. While much experimental data can be correlated by this hypothesis, it is possible that the ionophore concept may be more applicable to DNA and RNA structures that require counterion binding for stability.…”