Journal of the American Chemical Society, Vol.136, No.17, 6297-6305, 2014
Structure and Conformational Dynamics of a Stacked Dimeric G-Quadruplex Formed by the Human CEB1 Minisatellite
CEB1 is a highly polymorphic human minisatellite. In yeast, the size variation of CEB1 tandem arrays has been associated with the capacity of the motif to form G. quadruplexes. Here we report on the NMR solution structure of a G-quadruplex formed by the CEB1 DNA G-rich fragment d(AGGGGGGAGGGAGGGTGG), harboring several G-tracts including one with six continuous guanines. This sequence forms a dimeric G-quadruplex involving the stacking of two subunits, each being a unique snapback parallel-stranded scaffold with three G-tetrad layers, three double-chain-reversal loops, and a V-shaped loop. The two subunits are stacked at their S'-end tetrads, and multiple stacking rotamers may be present due to a high symmetry at the stacking interface. There is a conformational exchange in the millisecond time scale involving a swapping motion between two bases of the six-guanine tract. Our results not only add to the understanding of how the,G-quadruplex formation in human minisatellite leads to genetic instability but also address the fundamental questions regarding stacking of G-quadruplexes and how a long continuous G-tract participates in the structure and conformational dynamics of G-quadruplexes.