Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding

The folding kinetics is an important parameter affecting the relevance of DNA and RNA G-quadruplex (G4) structures in biological processes. Previous studies of the G4 folding kinetics mainly depended on fast measurement techniques. In previously available examples of G4s with loops up to three resid...

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Main Authors: Nguyen, Thi Quynh Ngoc, Lim, Kah Wai, Phan, Anh Tuân
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/150057
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1500572023-02-28T19:58:05Z Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding Nguyen, Thi Quynh Ngoc Lim, Kah Wai Phan, Anh Tuân School of Physical and Mathematical Sciences Science::Chemistry Science::Biological sciences::Biophysics Folding Kinetics G-quadruplex The folding kinetics is an important parameter affecting the relevance of DNA and RNA G-quadruplex (G4) structures in biological processes. Previous studies of the G4 folding kinetics mainly depended on fast measurement techniques. In previously available examples of G4s with loops up to three residues, the folding kinetics spanning several orders of magnitude has been reported, ranging from milliseconds to over 100 s. It is difficult to systematically and fundamentally understand the effect of multiple parameters, especially the loop properties, on the G4 folding kinetics, as the G4 fold is often altered when the sequence is varied. In this study, judicious choices of multiple parameters allowed us to bring various systems into the measurable window of a simple UV absorption technique. Using a well-controlled parallel-stranded G4 fold, we were able to systematically investigate the effect of seven different parameters of the environment and loop properties (temperature, K+ concentration, ionic strength, co-solute, loop length, loop sequence, and loop structure) on the G4 folding kinetics. We found that structured loops can drive up the G4 folding: for a long loop, the fast folding of a stem loop can guide the G4 folding and accelerate its folding kinetics by several orders of magnitude compared to an unstructured loop counterpart. Ministry of Education (MOE) National Research Foundation (NRF) Accepted version Singapore National Research Foundation Investigatorship (NRF-NRFI2017-09) Singapore Ministry of Education Academic Research Fund Tier 3 (MOE2012-T3-1-001) 2021-05-24T13:56:10Z 2021-05-24T13:56:10Z 2020 Journal Article Nguyen, T. Q. N., Lim, K. W. & Phan, A. T. (2020). Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding. The Journal of Physical Chemistry B, 124(25), 5122-5130. https://dx.doi.org/10.1021/acs.jpcb.0c02548 1520-6106 0000-0002-4970-3861 https://hdl.handle.net/10356/150057 10.1021/acs.jpcb.0c02548 32530285 2-s2.0-85087074709 25 124 5122 5130 en The Journal of Physical Chemistry B This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry B, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jpcb.0c02548 application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry
Science::Biological sciences::Biophysics
Folding Kinetics
G-quadruplex
spellingShingle Science::Chemistry
Science::Biological sciences::Biophysics
Folding Kinetics
G-quadruplex
Nguyen, Thi Quynh Ngoc
Lim, Kah Wai
Phan, Anh Tuân
Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding
description The folding kinetics is an important parameter affecting the relevance of DNA and RNA G-quadruplex (G4) structures in biological processes. Previous studies of the G4 folding kinetics mainly depended on fast measurement techniques. In previously available examples of G4s with loops up to three residues, the folding kinetics spanning several orders of magnitude has been reported, ranging from milliseconds to over 100 s. It is difficult to systematically and fundamentally understand the effect of multiple parameters, especially the loop properties, on the G4 folding kinetics, as the G4 fold is often altered when the sequence is varied. In this study, judicious choices of multiple parameters allowed us to bring various systems into the measurable window of a simple UV absorption technique. Using a well-controlled parallel-stranded G4 fold, we were able to systematically investigate the effect of seven different parameters of the environment and loop properties (temperature, K+ concentration, ionic strength, co-solute, loop length, loop sequence, and loop structure) on the G4 folding kinetics. We found that structured loops can drive up the G4 folding: for a long loop, the fast folding of a stem loop can guide the G4 folding and accelerate its folding kinetics by several orders of magnitude compared to an unstructured loop counterpart.
author2 School of Physical and Mathematical Sciences
author_facet School of Physical and Mathematical Sciences
Nguyen, Thi Quynh Ngoc
Lim, Kah Wai
Phan, Anh Tuân
format Article
author Nguyen, Thi Quynh Ngoc
Lim, Kah Wai
Phan, Anh Tuân
author_sort Nguyen, Thi Quynh Ngoc
title Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding
title_short Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding
title_full Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding
title_fullStr Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding
title_full_unstemmed Folding kinetics of G-quadruplexes : duplex stem loops drive and accelerate G-quadruplex folding
title_sort folding kinetics of g-quadruplexes : duplex stem loops drive and accelerate g-quadruplex folding
publishDate 2021
url https://hdl.handle.net/10356/150057
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