Structure of DNA tetrameric agcga-quadruplex adopted by
15-mer d(gcgagggagcgaggg), vk34, oligonucleotide found in
regulatory region of the plekhg3 human gene
Here we describe AGCGA-quadruplexes, an unexpected
addition to the well-known tetrahelical families,
G-quadruplexes and i-motifs, that have been a focus of
intense research due to their potential biological impact
in G- and C-rich DNA regions, respectively. High-resolution
structures determined by solution-state nuclear magnetic
resonance (NMR) spectroscopy demonstrate that
AGCGA-quadruplexes comprise four 5'-AGCGA-3' tracts and are
stabilized by G-A and G-C base pairs forming GAGA- and
GCGC-quartets, respectively. Residues in the core of the
structure are connected with edge-type loops. Sequences of
alternating 5'-AGCGA-3' and 5'-GGG-3' repeats could be
expected to form G-quadruplexes, but are shown herein to
form AGCGA-quadruplexes instead. Unique structural features
of AGCGA-quadruplexes together with lower sensitivity to
cation and pH variation imply their potential biological
relevance in regulatory regions of genes responsible for
basic cellular processes that are related to neurological
disorders, cancer and abnormalities in bone and cartilage
development.