| Abstract: |
The solution structure ofOxytrichatelomere sequence d[G4(T4G4)3] in 0.1 M Na+containing solution has been determined using a combined NMR-molecular dynamics approach including relaxation matrix refinement. This four G4repeat sequence folds intramolecularly into a right-handed G-tetraplex containing four stacked G-tetrads which are connected by two lateral T4loops and a central diagonal T4loop. The guanine glycosidic bonds adopt asyn-antialternation along the full length of the d[G4(T4G4)3] sequence while the orientation around adjacent G-tetrads switches betweensynsynantiantiandantiantisynsynalignments. Four distinct grooves are formed by the parallel (two of medium width) and anti-parallel (one wide and one narrow width) alignment of adjacent G-G-G-G segments in the G-tetraplex. The T4residues in the diagonal loop are well-defined while the T4residues in both lateral loops are under-defined and sample multiple conformations. The solution structure of the Na+-stabilizedOxytrichad[G4(T4G4)3] G-tetraplex and an earlier solution structure reported from our laboratory on the Na+-stabilized human d[AG3(T2AG3)3] G-tetraplex exhibit a common folding topology defined by the samesyn/antidistribution of guanine residues along individual strands and around individual G-tetrads, as well as a common central diagonal loop which defines the strand directionalities. The well-resolved proton NMR spectra associated with the d[G4(T4G4)3] G-tetraplex opens the opportunity for studies ranging from cation-dependent characterization of G-tetraplex conformation and hydration to ligand and protein recognition of the distinct grooves associated with this folding topology.f2 f2 Abbreviations used: NOE, nuclear Overhauser enhancement, NOESY, NOE spectroscopy; r.m.s.d, rot-mean-square deviation; MMDG, metric matric distance geometry; SA, simulated annealing; MD, molecular dynamics. © 1995 Academic Press Limited. |
