A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats 1 1Edited by I. Tinoco - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Molecular Biology Année : 1998

A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats 1 1Edited by I. Tinoco

Abdelali Kettani
  • Fonction : Auteur
Dinshaw Patel
  • Fonction : Auteur

Résumé

We have identified a unique structural transition (in slow exchange on the NMR time scale) in the tertiary fold of the d(G-G-G-C-T4-G-G-G-C) quadruplex on proceeding from Na+ to K+ as counterion in aqueous solution. Both monovalent cation-dependent conformations exhibit certain common structural features, which include head-to-tail dimerization of two symmetry-related stem-hairpin loops, adjacent strands which are antiparallel to each other and adjacent stacked G(syn).G(anti). G(syn).G(anti) tetrads in the central core of the quadruplexes. The Na and K cation stabilized structures of the d(G-G-G-C-T4-G-G-G-C) quadruplexes differ in the conformations of the T-T-T-T loops, the relative alignment of G.C base-pairs positioned opposite each other through their major groove edges and potentially in the number of monovalent cation binding sites. We have identified potential K cation binding cavities within the symmetry-related T-T-T-G segments, suggesting the potential for two additional monovalent cation binding sites in the K cation-stabilized quadruplex relative to its Na cation-stabilized counterpart. Modeling studies suggest that the major groove edges of guanine residues in Watson-Crick G.C base-pairs could potentially be bridged by coordinated K cations in the d(G-G-G-C-T4-G-G-G-C) quadruplex in KCl solution in contrast to formation of G.C.G.C tetrads for the corresponding quadruplex in NaCl solution. Our results defining the molecular basis of a Na to K cation-dependent conformational switch in the loop spanning segment of the d(G-G-G-C-T4-G-G-G-C) quadruplex may have relevance to recent observations that specific K cation coordinated loop conformations within quadruplexes exhibit inhibitory activity against HIV integrase.

Dates et versions

hal-02122553 , version 1 (07-05-2019)

Identifiants

Citer

A. Bouaziz, Abdelali Kettani, Dinshaw Patel, Serge Bouaziz. A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats 1 1Edited by I. Tinoco. Journal of Molecular Biology, 1998, 282 (3), pp.637-652. ⟨10.1006/jmbi.1998.2031⟩. ⟨hal-02122553⟩
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