Structure of a Stable G-Hairpin

Abstract

In this study, we report the first atomic resolution structure of a stable G-hairpin formed by a natively occurring DNA sequence. An 11-nt long G-rich DNA oligonucleotide, 5'-d(GTGTGGGTGTG)-3', corresponding to the most abundant sequence motif in irregular telomeric DNA from Saccharomyces cerevisiae (yeast), is demonstrated to adopt a novel type of mixed parallel/antiparallel fold-back DNA structure, which is stabilized by dynamic G:G base pairs that transit between N1-carbonyl symmetric and N1-carbonyl, N7-amino base-pairing arrangements. Although the studied sequence first appears to possess a low capacity for base pairing, it forms a thermodynamically stable structure with a rather complex topology that includes a chain reversal arrangement of the backbone in the center of the continuous G-tract and 3'-to-5' stacking of the terminal residues. The structure reveals previously unknown principles of the folding of G-rich oligonucleotides that could be applied to the prediction of natural and/or the design of artificial recognition DNA elements. The structure also demonstrates that the folding landscapes of short DNA single strands is much more complex than previously assumed.

A Minimal Sequence for Left‐Handed G‐Quadruplex Formation

“…[9] Diverse new G-quadruplex folds have been found recently,i ncluding G-quadruplexes with bulges [10] and duplex hairpins. [11] Related alternative conformations of G-rich DNAi nclude ah airpin, [12] triplex, [13] and alternative tetraplex. [14] Bioinformatic and sequencing analyses show that G-quadruplexes are present in important regulatory region of the human genome.…”

A Minimal Sequence for Left‐Handed G‐Quadruplex Formation

“…[6] Thestructural variability observed for G-quadruplexes depends on the primary sequence, [7] ions type, [6b,c] salt concentration, [8] and environment. [11] Related alternative conformations of G-rich DNAi nclude ah airpin, [12] triplex, [13] and alternative tetraplex. [11] Related alternative conformations of G-rich DNAi nclude ah airpin, [12] triplex, [13] and alternative tetraplex.…”

Harnessing intrinsic fluorescence for typing of secondary structures of DNA

“…Subsequently, we tested a number of sequences adopting secondary structures other than those represented in the training set. These include the stacked dimeric G4 structure known 510 to be the most fluorescent unmodified oligonucleotide described to date (G3T) (25,28,41), three left-handed G4 structures (ZG4, Block2Δ, 2xBlock2) (44,45), three peculiar non-G4 quadruple helices (VK1, VK2, VK34) (46,47), two A-type duplexes ((G3C3)3 and (G3C3)2) (48,49), a G-hairpin (SC11) (50), and three supposed single strands displaying peculiar CD signatures, namely ss8, 24non096 and scr26 (Table S4). The CD spectra of these 515 sequences in buffers A and B are presented in Figure S18.…”