Structure of a Stable G‑Hairpin

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.