Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion

Understanding the mechanism of Na+/K+-dependent spectral conversion of human telomeric G-quadruplex (G4) sequences has been limited not only because of the structural polymorphism but also the lack of sufficient structural information at different stages along the conversion process for one given ol...

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Main Authors: Wang, Zi-Fu, Li, Ming-Hao, Hsu, Shang-Te Danny, Chang, Ta-Chau
Format: Online
Language:English
Published: Oxford University Press 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985656/
id pubmed-3985656
recordtype oai_dc
spelling pubmed-39856562014-04-18 Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion Wang, Zi-Fu Li, Ming-Hao Hsu, Shang-Te Danny Chang, Ta-Chau Structural Biology Understanding the mechanism of Na+/K+-dependent spectral conversion of human telomeric G-quadruplex (G4) sequences has been limited not only because of the structural polymorphism but also the lack of sufficient structural information at different stages along the conversion process for one given oligonucleotide. In this work, we have determined the topology of the Na+ form of Tel23 G4, which is the same hybrid form as the K+ form of Tel23 G4 despite the distinct spectral patterns in their respective nuclear magnetic resonance (NMR) and circular dichroism spectra. The spectral difference, particularly the well-resolved imino proton NMR signals, allows us to monitor the structural conversion from Na+ form to K+ form during Na+/K+ exchange. Time-resolved NMR experiments of hydrogen–deuterium exchange and hybridization clearly exclude involvement of the global unfolding for the fast Na+/K+ spectral conversion. In addition, the K+ titration monitored by NMR reveals that the Na+/K+ exchange in Tel23 G4 is a two-step process. The addition of K+ significantly stabilizes the unfolding kinetics of Tel23 G4. These results offer a possible explanation of rapid spectral conversion of Na+/K+ exchange and insight into the mechanism of Na+/K+ structural conversion in human telomeric G4s. Oxford University Press 2014-04 2014-01-28 /pmc/articles/PMC3985656/ /pubmed/24476914 http://dx.doi.org/10.1093/nar/gku083 Text en © The Author(s) 2014. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Wang, Zi-Fu
Li, Ming-Hao
Hsu, Shang-Te Danny
Chang, Ta-Chau
spellingShingle Wang, Zi-Fu
Li, Ming-Hao
Hsu, Shang-Te Danny
Chang, Ta-Chau
Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion
author_facet Wang, Zi-Fu
Li, Ming-Hao
Hsu, Shang-Te Danny
Chang, Ta-Chau
author_sort Wang, Zi-Fu
title Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion
title_short Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion
title_full Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion
title_fullStr Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion
title_full_unstemmed Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion
title_sort structural basis of sodium–potassium exchange of a human telomeric dna quadruplex without topological conversion
description Understanding the mechanism of Na+/K+-dependent spectral conversion of human telomeric G-quadruplex (G4) sequences has been limited not only because of the structural polymorphism but also the lack of sufficient structural information at different stages along the conversion process for one given oligonucleotide. In this work, we have determined the topology of the Na+ form of Tel23 G4, which is the same hybrid form as the K+ form of Tel23 G4 despite the distinct spectral patterns in their respective nuclear magnetic resonance (NMR) and circular dichroism spectra. The spectral difference, particularly the well-resolved imino proton NMR signals, allows us to monitor the structural conversion from Na+ form to K+ form during Na+/K+ exchange. Time-resolved NMR experiments of hydrogen–deuterium exchange and hybridization clearly exclude involvement of the global unfolding for the fast Na+/K+ spectral conversion. In addition, the K+ titration monitored by NMR reveals that the Na+/K+ exchange in Tel23 G4 is a two-step process. The addition of K+ significantly stabilizes the unfolding kinetics of Tel23 G4. These results offer a possible explanation of rapid spectral conversion of Na+/K+ exchange and insight into the mechanism of Na+/K+ structural conversion in human telomeric G4s.
publisher Oxford University Press
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985656/
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