Small Change in a G-Rich Sequence, a Dramatic Change in Topology: New Dimeric G-Quadruplex Folding Motif with Unique Loop Orientations

Abstract

NMR study has shown that DNA oligonucleotide d(G₃T₄G₄) adopts an asymmetric bimolecular G-quadruplex structure in solution. The structure of d(G₃T₄G₄)₂ is composed of three G-quartets, overhanging G11 residue and G3, which is part of the loop. Unique structural feature of d(G₃T₄G₄)₂ fold is the orientation of the two loops. Thymidine residues T4-T7 form a diagonal loop, whereas T15-T18 form an edge type loop. The G-quadruplex core of d(G₃T₄G₄)₂ consists of two stacked G-quartets with syn-anti-anti-anti alternation of dG residues and one G-quartet with syn-syn-anti-anti alternation. Another unusual structural feature of d(G₃T₄G₄)₂ is a leap between G19 and G20 over the middle G-quartet and chain reversal between G19 and G20 residues. The presence of one antiparallel and three parallel strands reveals the hitherto unknown G-quadruplex folding motif consisting of antiparallel/parallel strands and diagonal as well as edge type loops. Further examination of the influence of different monovalent cations on the folding of d(G₃T₄G₄) showed that it forms a bimolecular G-quadruplex in the presence of K⁺, Na⁺, and NH₄⁺ ions with the same general fold.