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 constrained molecular dynamics shows excellent compatibility with the observed nuclear Overhauser effects (NOEs) particularly for the very unusual inter-residue sugar-sugar NOEs H1'-H1', H1'-H2" and H1'-H4'. These NOEs are probably diagnostic for such tetrameric structures.

Interactions of cryptolepine and neocryptolepine with unusual DNA structures

“…The recent discovery of positively charged aromatic compounds (for a review [21]) that interact with G-quartet led us to test the binding of cryptolepine and neocryptolepine analogues to G-quadruplexes. A cytidine-rich oligomer forms a radically different quadruplex in which two parallel C-strands associate in a head-to-tail orientation with their C•C + pairs face-to-face, intercalated in a so called i-motif or C-quadruplex [22,23].…”

Human chromosomal centromere (AATGG)n sequence forms stable structures with unusual base pairs

“…A number of recent studies have revealed that simple short repeats of DNA sequences, like (C-G)~ [4], (C-A)n [5], the telomere repeat, (TTGGGG)n [6,7], (CGA)~ [8,9] and d(TCCCCC) [10], often are associated with unusual DNA structures that may play important biological roles. Here we analyzed in detail the structures associated with the (AATGG)~ sequence by two-dimensional nuclear magnetic resonance spectroscopy (2D NMR) through a quantitative treatment of the nuclear Overhauser effect (NOE) data.…”

Ultrafast excited-state dynamics of RNA and DNA C tracts

“…It has been assumed in the past that poly(rC) and poly(dC) form hemiprotonated duplexes [36], but there is no decisive structural proof. About fifteen years ago, NMR [27,50] and later x-ray crystal structures [51,52] showed that dC-rich oligonucleotides adopt a quadruplex form ("i-motif DNA") composed of two intercalated duplexes, each of which consists of CH + ·C base pairs. Crystals of d(CT) 3 grown at neutral pH adopt the quadruplex structure [52], showing that i-motif structures do not require acidic conditions for deoxycytidylates.…”

“…It was proposed more than forty years ago that poly(rC) can adopt a double-stranded conformation with parallel strands when the pH is between 4 and 6 [25,26]. More recently, structural NMR studies have shown that cytosine-rich DNAs form an unusual quadruplex structure ("i-motif DNA") consisting of two intercalated duplexes made up of hemiprotonated base pairs [27,28]. This structure, which may be biologically significant [29][30][31], is formed when two parallel-stranded duplexes associate in head-to-tail fashion, forming intercalated hemiprotonated base pairs.…”