Book of Abstracts: Albany 2003
June 17-21 2003
Ions, Solvent and Counter-ions in G-quadruplex Structures
Guanine-rich sequences of nucleic acids can readily associate to form four-stranded structures, quadruplexes, whose underlying motif is the Hoogsteen hydrogen-bonded guanine quartet. The non-guanine tracts in sequences such as that of the human telomere repeat d(TTAGGG), generally form non-helical loop structures attached in some way to the core quadruplex. The discovery of parallel intramolecular quadruplexes (1), showed that the diversity of quadruplex folds is greater than anticipated, and also that the nature of the loops plays a major role in defining the fold.
Quadruplex folding and stability is dependent on metal ions, notably the alkaline metals Na+ and K+. We have now determined the crystal structures of six quadruplex complexes, and from this data set is emerging a picture of the structural roles played by these ions. The structural data is being complemented by molecular dynamics simulations, which are providing a picture of the relative mobilities of these ions. Data from these structural and computational approaches will be presented at the meeting.
Shozeb M Haider
Cancer Research UK Biomolecular Structure Group