Diagonal loops

An additional constraint for the folding topologies for bimolecular and inter-molecular quadruplexes relates to the number (length) of the linking nucleotides. Short linker lengths, two or less, will prevent diagonal loops from forming due to the distance to be spanned across G tetrad. However, the short... 

The first indication that several conformations could be observed came from the comparison of the NMR solution and an earlier X-ray structure of the Oxytricha bimolecular quadruplex. The initial X-ray structure contained many of the features found in the solution structure but differed in the orientation of the thymine loops edge-loops were observed by X-ray as compared to diagonal-loops in the NMR structure. However, a recent analysis corrected this earlier crystallographic study and demonstrated that this quadruplex adopts a structure with two strands forming an antiparallel diagonal arrangement, indicating that the native structure is the same in solution and in the crystalline state. 

The most striking and recent example of structural complexity is the intramolecular human telomeric motif. In sodium, the AG3(T2AG3)3 sequence adopts an intramolecular fold with a central diagonal loop. As a result, each strand has one parallel and one antiparallel neighbour. In potassium, the situation is different. Crystallographic studies indicate that the very same sequence adopts a completely different folding scheme all four DNA strands are parallel, with the three linking trinucleotide loops positioned on the exterior... 

Figure 2 Schematic and representative structures of different loops in G-quadruplexes (a) edgewise loop, (b) diagonal loop, (c) double-chain-reversal loop, and (d) V-shaped loop...

V-shaped loops connecting two corners of a G-tetrad core in which one supporting column is lacking [Figure 2(d)]. The types of loops depend strongly on the size and sequence of the linkers. Diagonal loops eontain three or more residues.Besides one example of a quadruplex with mixed tetrads,in... 

The d(A2G2T4A2G2) sequence forms a diamond-shaped dimeric G-quadru-plex" with diagonal loops (Figure 4). Formation of a T (A-A) triad [Figure 4(c)] was observed in the A2T4 diagonal loops. This triad is stabilized by stacking on the G-tetrad core. 

Formation of a G (A-G) triad in the context of the GAAG diagonal loop is discussed in paragraph 3.3.9 below. 

Figure 4 Structure of the d(A2G2T4A2G2) diamond-shaped dimeric G-quadruplex with triad-containing diagonal loops.(a) Ribbon and (b) schematic view of the structure, (c) Alignment ofT-(A-A) triad...

R. Jones and D.J. Patel, 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... 

A systematic study of G-rich oligonucleotides containing runs of G residues of various lengths, and with varying numbers intervening residues, revealed a cation-dependent pattern for the G-quadruplex folds adopted by these sequences. It was shown that ions are required to stabilize chair type structures, that is, G-quadruplexes with lateral loops instead of diagonal loops. A minimum of three residues in the central loop and two residues in the two outer loops is required to form an intramolecular chair-type quadruplex, otherwise a mixture of tetramolecular parallel-stranded quadruplexes is... 

Thomas and co-workers used Raman spectroscopy to generate a phase diagram of antiparallel and parallel G-quadruplex structures as controlled by concentrations of Na and K " ions. Both alkali ions facilitate the formation of an antiparallel diagonal-loop G-quadruplex by four units of the telomere repeat sequence of O. nova, d(T4G4)4, at low concentrations. An extended, parallel-stranded tetramolecular G-quadruplex is formed at higher cation concentrations. However, K " is more effective than Na in inducing the parallel strand association. The midpoints of the Na " and K concentrations required for the structural transition are 225 and 65 mM, respectively. ... 

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