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bioRxiv · 10.1101/526780

Folding landscape of a parallel G-quadruplex

Gray, R. D.·Trent, J. O.·Arumugam, S.·Chaires, J.
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Abstract

Circular dichroism and stopped-flow UV spectroscopies were used to investigate the thermodynamic stability and the folding pathway of d(TGAG3TG3TAG3TG3TA2) at 25C in solutions containing 25 mM KCl. Under these conditions the oligonucleotide adopts a thermally stable, all-parallel G-quadruplex topography containing three stacked quartets. K+-induced folding shows three resolved relaxation times, each with distinctive spectral changes. Folding is complete within 200 s. These data indicate a folding pathway that involves at least two populated intermediates, one of which seems to be an antiparallel structure that rearranges to the final all-parallel conformation. Molecular dynamics reveals a stereochemically plausible folding pathway that does not involve complete unfolding of the intermediate. The rate of unfolding was determined using complementary DNA to trap transiently unfolded states to form a stable duplex. As assessed by 1D-1H NMR and fluorescence spectroscopy, unfolding is extremely slow with only one observable rate-limiting relaxation time.

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Gray, R. D., Trent, J. O., Arumugam, S., Chaires, J.. 2019-01-22. Folding landscape of a parallel G-quadruplex. https://doi.org/10.1101/526780

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