A diamond-shaped zipper-like DNA architecture containing triads sandwiched between mismatches and tetrads Journal Article
| Authors: | Kuryavyi, V.; Kettani, A.; Wang, W.; Jones, R.; Patel, D. J. |
| Article Title: | A diamond-shaped zipper-like DNA architecture containing triads sandwiched between mismatches and tetrads |
| Abstract: | The present study reports on the solution structure of the guanine plus adenine rich d(A2G2T4A2G2) 12-mer sequence which forms a unique fold in moderate NaCl solution. Proton resonance assignments for this sequence, which contains a pair of AAGG repeats separated by a T4 linker segment, were aided by site-specific 15N-labeling of guanine and adenine bases, as well as site-specific incorporation of 2,6-diaminopurine and 8-bromoadenine for adenine, 8-bromoguanine, 7-deazaguanine and inosine for guanine, and uracil and 5-bromouracil for thymine. The solution structure, which was solved by a combined NMR and intensity-refined computational approach, consists of a diamond-shaped architecture formed through dimerization of a pair of d(A2G2T4A2G2) hairpins. This 2-fold symmetric structure contains a quadruplex core consisting of a pair of symmetry-related G(syn)·G(syn)·G(anti)·G(anti) tetrads, where adjacent strands have both parallel and anti-parallel neighbors and connecting T4 segments which form diagonal loops. Each of the G(syn)·G(syn)·G(anti)·G(anti) tetrads forms a platform on which stacks a T(anti)·[A(syn)-A(anti)] triad containing a novel A(syn)-A(anti) platform step and a reversed Hoogsteen A(syn)·T(anti) pair. We observe both base-base and base-sugar stacking interactions, with the latter occuring at a sheared A-G step where the sugar of the A stacks on the purine plane of the G. Unexpectedly, the topology of this sheared A(anti)-G(syn) step has many similarities with the C(anti)-G(syn) step in left-handed Z-DNA. The T·(A-A) triad is sandwiched between the G-tetrad on one side and a reversed Hoogsteen A(anti)·T(anti) pair on the other. This intercalative topology is facilitated by a zipper-like motif where the A(anti) residue of the triad is interdigitated within a stretched A(anti)-G(syn) step. Our structural study reports on new aspects of A-A platforms, base triads, zipper-like interdigitation and sheared base steps, together with base-base and base-sugar stacking defining a diamond-like architecture for the d(A2G2T4A2G2) sequence. One can anticipate that mixed guanine-adenine sequences will exhibit a rich diversity of polymorphic architectures that will provide unique topologies for recognition by both nucleic acids and proteins. (C) 2000 Academic Press. |
| Keywords: | dna; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; dna structure; models, molecular; protons; dimerization; nucleic acid conformation; structure analysis; dna determination; stoichiometry; phosphorus; nucleic acid base substitution; nuclear overhauser effect; priority journal; article; a(syn)-a(anti) platform; g-tetrad; multi-stranded dna architecture; t·(a-a) triad; zipper motif |
| Journal Title: | Journal of Molecular Biology |
| Volume: | 295 |
| Issue: | 3 |
| ISSN: | 0022-2836 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 2000-01-21 |
| Start Page: | 455 |
| End Page: | 469 |
| Language: | English |
| DOI: | 10.1006/jmbi.1999.3345 |
| PUBMED: | 10623538 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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