A double chain reversal loop and two diagonal loops define the architecture of a unimolecular DNA quadruplex containing a pair of stacked G(syn)·G(syn)·G(anti)·G(anti) tetrads flanked by a G·(T-T) triad and a T·T·T triple

Vitaly Kuryavyi, Ananya Majumdar, Anthony Shallop, Natalya Chernichenko, Eugene Skripkin, Roger Jones, Dinshaw J. Patel

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

The architecture of G·G·G·G tetrad-aligned DNA quadruplexes in monovalent cation solution is dependent on the directionality of the four strands, which in turn are defined by loop connectivities and the guanine. syn/anti distribution along individual strands and within individual G·G·G·G tetrads. The smallest unimolecular G-quadruplex belongs to the d(G2NnG2 NnG2NnG2) family, which has the potential to form two stacked G-tetrads linked by Nn loop connectivities. Previous studies have focused on the thrombin-binding DNA aptamer d(G2T2G2 TGTG2T2G2), where Nn was T2 for the first and third connecting loops and TGT for the middle connecting loop. This DNA aptamer in K+ cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)·G(anti)·G(syn)·G(anti) tetrads, adjacent strands which are antiparallel to each other and edge-wise connecting T2, TGT and T2 loops. We now report on the NMR-based solution structure of the d(G2T4G2 CAG2GT4G2T) sequence, which differs from the thrombin-binding DNA aptamer sequence in having longer first (T4) and third (GT4) loops and a shorter (CA) middle loop. This d(G2T4G2 CAG2GT4G2T) sequence in Na+ cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)·G(syn)·G(anti)·G(anti) tetrads, adjacent strands which have one parallel and one antiparallel neighbors and distinct non-edge-wise loop connectivities. Specifically, the longer first (T4) and third (GT4) loops are of the diagonal type while the shorter middle loop is of the double chain reversal type. In addition, the pair of stacked G·G·G·G tetrads are flanked on one side by a G·(T-T) triad and on the other side by a T·T·T triple. The distinct differences in strand directionalities, loop connectivities and syn/anti distribution within G·G·G·G tetrads between the thrombin-binding DNA aptamer d(G2T2G2 TGTG2T2G2) quadruplex reported previously, and the d(G2T4G2 CAG2GT4G2T) quadruplex reported here, reinforces the polymorphic nature of higher-order DNA architectures. Further, these two small unimolecular G-quadruplexes, which are distinct from each other and from parallel-stranded G-quadruplexes, provide novel targets for ligand recognition. Our results demonstrate that the double chain reversal loop connectivity identified previously by our laboratory within the Tetrahymena telomere d(T2G4)4 quadruplex, is a robust folding topology, since it has now also been observed within the d(G2T4G2 CAG2GT4G2T) quadruplex. The identification of a G·(T-T) triad and a T·T·T triple, expands on the available recognition alignments for base triads and triples.

Original languageEnglish (US)
Pages (from-to)181-194
Number of pages14
JournalJournal of molecular biology
Volume310
Issue number1
DOIs
StatePublished - Jun 29 2001

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

  • Diagonal loops
  • Double chain reversal loop
  • G(syn)·G(syn)·G(anti)·G(anti) tetrads
  • G·(T-T) triad
  • T·T·T triple
  • Unimolecular G-quadruplex

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