Kinetics and mechanism of conformational changes in a G-quadruplex of thrombin-binding aptamer induced by Pb2+

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

48 Scopus Citations
View graph of relations

Author(s)

  • Tai-Chu Lau
  • Haojun Liang

Detail(s)

Original languageEnglish
Pages (from-to)13051-13056
Journal / PublicationJournal of Physical Chemistry B
Volume115
Issue number44
Publication statusPublished - 10 Nov 2011

Abstract

It has been shown that guanine-rich DNA can fold into a G-quadruplex with certain metal cations. The spectral characteristics, thermostability, and kinetics for the formation of a Pb2+-driven G-quadruplex of thrombin-binding aptamer (TBA) were measured in the current work using a combination of ultraviolet (UV) and circular dichroism (CD) spectroscopy along with stopped-flow technique. CD spectra demonstrated that TBA could fold into a unique G-quadruplex with a strong positive peak at 312 nm. Analysis of the titration data reveals that the binding stoichiometry is 1:1 for the titration of TBA with Pb(NO3)2, which is in accordance with the localization of the Pb2+ ion between the adjacent G-quartets. Thermal denaturation profiles indicate that the Pb2+-induced intramolecular G-quadruplex is more stable than those driven by Na+ or K+ ions. Kinetic studies suggest that the Pb2+-induced folding G-quadruplex of TBA probably proceeds through the rapid formation of an intermediate Pb2+-TBA complex, which then isomerizes to the fully folded structure. Conformational changes transpire after the addition of Pb(NO3)2 to the Na+- or K+-induced G-quadruplexes, which may be attributed to the replacement of Na+ or K+ ions by Pb2+ ions and the generation of a more compact structure of the Pb2+-TBA structure. The relaxation time, τ, of folding the G-quadruplex is reduced from 1.05 s in the presence of Pb 2+ ions alone to 0.34 s under the cooperation of initially added Na+ ions, while τ is increased to 8.33 s under the competition of initially added K+ ions. © 2011 American Chemical Society.

Citation Format(s)

Kinetics and mechanism of conformational changes in a G-quadruplex of thrombin-binding aptamer induced by Pb2+. / Liu, Wei; Fu, Yan; Zheng, Bin et al.
In: Journal of Physical Chemistry B, Vol. 115, No. 44, 10.11.2011, p. 13051-13056.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review