A tetrameric DNA structure with protonated cytosine-cytosine base pairs

Abstract

OLIGOMERS containing tracts of cytidine form hemiprotonated base pairs at acid pH and have been considered to be double-stranded. We have solved the structure of the DNA oligomer 5′-d(TCCCCC) at acid pH and find that it is a four-stranded complex in which two base-paired parallel-stranded duplexes are intimately associated, with their base pairs fully intercalated. The relative orientation of the duplexes is antiparallel, so that each base pair is face-to-face with its neighbours. The NMR spectrum displays only six spin systems, showing that the structure is highly symmetrical on the NMR timescale; the four strands are equivalent. A model derived by energy minimization and con-strained molecular dynamics shows excellent compatibility with the observed nuclear Overhauser effects (NOEs) particularly for the very unusual inter-residue sugar-sugar NOEs HI′-HI′, Hl′-H2" and H1′-H4′. These NOEs are probably diagnostic for such tetrameric structures.