G-quadruplex conformation and dynamics are determined by loop length and sequence

The quadruplex forming G-rich sequences are unevenly distributed throughout the human genome. Their enrichment in oncogenic promoters and telomeres has generated interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we present a quantitative analysis on the conformations and dynam...

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Main Authors:	Tippana, Ramreddy, Xiao, Weikun, Myong, Sua
Format:	Online
Language:	English
Published:	Oxford University Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081081/

id	pubmed-4081081
recordtype	oai_dc
spelling	pubmed-40810812014-07-10 G-quadruplex conformation and dynamics are determined by loop length and sequence Tippana, Ramreddy Xiao, Weikun Myong, Sua Structural Biology The quadruplex forming G-rich sequences are unevenly distributed throughout the human genome. Their enrichment in oncogenic promoters and telomeres has generated interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we present a quantitative analysis on the conformations and dynamics of GQ forming sequences measured by single molecule fluorescence. Additionally, we relate these properties to GQ targeting ligands and G4 resolvase 1 (G4R1) protein binding. Our result shows that both the loop (non-G components) length and sequence contribute to the conformation of the GQ. Real time single molecule traces reveal that the folding dynamics also depend on the loop composition. We demonstrate that GQ-stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and the G4R1 protein bind selectively to the parallel GQ conformation. Our findings point to the complexity of GQ folding governed by the loop length and sequence and how the GQ conformation determines the small molecule and protein binding propensity. Oxford University Press 2014-08-01 2014-06-11 /pmc/articles/PMC4081081/ /pubmed/24920827 http://dx.doi.org/10.1093/nar/gku464 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. 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	Tippana, Ramreddy Xiao, Weikun Myong, Sua
spellingShingle	Tippana, Ramreddy Xiao, Weikun Myong, Sua G-quadruplex conformation and dynamics are determined by loop length and sequence
author_facet	Tippana, Ramreddy Xiao, Weikun Myong, Sua
author_sort	Tippana, Ramreddy
title	G-quadruplex conformation and dynamics are determined by loop length and sequence
title_short	G-quadruplex conformation and dynamics are determined by loop length and sequence
title_full	G-quadruplex conformation and dynamics are determined by loop length and sequence
title_fullStr	G-quadruplex conformation and dynamics are determined by loop length and sequence
title_full_unstemmed	G-quadruplex conformation and dynamics are determined by loop length and sequence
title_sort	g-quadruplex conformation and dynamics are determined by loop length and sequence
description	The quadruplex forming G-rich sequences are unevenly distributed throughout the human genome. Their enrichment in oncogenic promoters and telomeres has generated interest in targeting G-quadruplex (GQ) for an anticancer therapy. Here, we present a quantitative analysis on the conformations and dynamics of GQ forming sequences measured by single molecule fluorescence. Additionally, we relate these properties to GQ targeting ligands and G4 resolvase 1 (G4R1) protein binding. Our result shows that both the loop (non-G components) length and sequence contribute to the conformation of the GQ. Real time single molecule traces reveal that the folding dynamics also depend on the loop composition. We demonstrate that GQ-stabilizing small molecules, N-methyl mesoporphyrin IX (NMM), its analog, NMP and the G4R1 protein bind selectively to the parallel GQ conformation. Our findings point to the complexity of GQ folding governed by the loop length and sequence and how the GQ conformation determines the small molecule and protein binding propensity.
publisher	Oxford University Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081081/
_version_	1613107898816135168

G-quadruplex conformation and dynamics are determined by loop length and sequence

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