A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats Journal Article
| Authors: | Bouaziz, S.; Kettani, A.; Patel, D. J. |
| Article Title: | A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats |
| Abstract: | 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. |
| Keywords: | dna; binding site; dna structure; models, molecular; dimerization; binding sites; molecular structure; conformational transition; nucleic acid conformation; repetitive sequences, nucleic acid; potassium; integrase; potassium ion; tandem repeat; sodium ion; monovalent cation; hiv integrase; humans; priority journal; article; g-g-g-c repeat-containing dna quadruplexes; dna quadruplexes targeted to hiv integrase; monovalent cation-dependent conformational transitions; potential k cation coordination sites; potential k cation encapsulation within a hairpin loop |
| Journal Title: | Journal of Molecular Biology |
| Volume: | 282 |
| Issue: | 3 |
| ISSN: | 0022-2836 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 1998-09-25 |
| Start Page: | 637 |
| End Page: | 652 |
| Language: | English |
| DOI: | 10.1006/jmbi.1998.2031 |
| PUBMED: | 9737927 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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