ja4125274_si_001.pdf (2.47 MB)
Structure and Conformational Dynamics of a Stacked Dimeric G‑Quadruplex Formed by the Human CEB1 Minisatellite
journal contribution
posted on 2014-04-30, 00:00 authored by Michael Adrian, Ding Jie Ang, Christopher
J. Lech, Brahim Heddi, Alain Nicolas, Anh Tuân PhanCEB1 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
5′-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.