Double helix is the most known structure of DNA. It can account for transfer of genetic information. However, DNA can fold into a wide range of structures that are associated with its unique biological roles and functions. G-rich DNA segments adopting to d[G≥3N1–7G≥3N1–7G≥3N1–7G≥3] motif are populated in hundreds of thousands and have the potential to form a G-quadruplex structure. G-rich fragments from the PLEKHG3 gene can form tetrahelical structures that differ significantly from G-quadruplexes, despite containing the G-quadruplex folding motif d[G3NG3NG3NG3], where N=AGCGA. These sequences adopt tetrahelical cores of AGCGA repeats, connected with edge-type loops of G–G base pairs. A marked difference between G- and AGCGA-quadruplexes is their opposing response to changes in water activity. While the former become stabilized with decreasing water activity, the reverse is true for the latter (and B-DNA).
Another intriguing case when relying on sequence details alone to predict G-quadruplex structure was reported recently on a G-rich sequence found in the regulatory region of the RANKL gene, associated with homeostasis of bone metabolism. An oligonucleotide with four G-tracts of three successive guanine residues folds into a two-quartet basket-type G-quadruplex.
d[(G4C2)3G4] implicated in neurological disorders ALS and FTD forms two major G-quadruplex structures. Structural characterization of the G-quadruplex named AQU revealed an antiparallel fold composed of four G-quartets and three lateral C–C loops. Two C•C base pairs are stacked on the nearby G-quartet and are involved in a dynamic equilibrium between symmetric N3-amino and carbonyl-amino geometries and protonated C+•C state.
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