Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation

Abstract Recently, non-canonical DNA structures, such as G-quadruplexes (GQs), were found to be highly pressure sensitive, suggesting that pressure modulation studies can provide additional mechanistic details of such biomolecular systems. Using FRET and CD spectroscopy as well as binding equilibriu...

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Autores principales:	Rosario Oliva, Sanjib Mukherjee, Roland Winter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/94c9a90a87ed4256a5459e738bc7c9de
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spelling	oai:doaj.org-article:94c9a90a87ed4256a5459e738bc7c9de2021-12-02T14:29:15ZUnraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation10.1038/s41598-021-89215-22045-2322https://doaj.org/article/94c9a90a87ed4256a5459e738bc7c9de2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89215-2https://doaj.org/toc/2045-2322Abstract Recently, non-canonical DNA structures, such as G-quadruplexes (GQs), were found to be highly pressure sensitive, suggesting that pressure modulation studies can provide additional mechanistic details of such biomolecular systems. Using FRET and CD spectroscopy as well as binding equilibrium measurements, we investigated the effect of pressure on the binding reaction of the ligand ThT to the quadruplex 22AG in solutions containing different ionic species and a crowding agent mimicking the intracellular milieu. Pressure modulation helped us to identify the different conformational substates adopted by the quadruplex at the different solution conditions and to determine the volumetric changes during complex formation and the conformational transitions involved. The magnitudes of the binding volumes are a hallmark of packing defects and hydrational changes upon ligand binding. The conformational substates of the GQ as well as the binding strength and the stoichiometry of complex formation depend strongly on the solution conditions as well as on pressure. High hydrostatic pressure can also impact GQs inside living cells and thus affect expression of genetic information in deep sea organisms. We show that sub-kbar pressures do not only affect the conformational dynamics and structures of GQs, but also their ligand binding reactions.Rosario OlivaSanjib MukherjeeRoland WinterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rosario Oliva Sanjib Mukherjee Roland Winter Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation
description	Abstract Recently, non-canonical DNA structures, such as G-quadruplexes (GQs), were found to be highly pressure sensitive, suggesting that pressure modulation studies can provide additional mechanistic details of such biomolecular systems. Using FRET and CD spectroscopy as well as binding equilibrium measurements, we investigated the effect of pressure on the binding reaction of the ligand ThT to the quadruplex 22AG in solutions containing different ionic species and a crowding agent mimicking the intracellular milieu. Pressure modulation helped us to identify the different conformational substates adopted by the quadruplex at the different solution conditions and to determine the volumetric changes during complex formation and the conformational transitions involved. The magnitudes of the binding volumes are a hallmark of packing defects and hydrational changes upon ligand binding. The conformational substates of the GQ as well as the binding strength and the stoichiometry of complex formation depend strongly on the solution conditions as well as on pressure. High hydrostatic pressure can also impact GQs inside living cells and thus affect expression of genetic information in deep sea organisms. We show that sub-kbar pressures do not only affect the conformational dynamics and structures of GQs, but also their ligand binding reactions.
format	article
author	Rosario Oliva Sanjib Mukherjee Roland Winter
author_facet	Rosario Oliva Sanjib Mukherjee Roland Winter
author_sort	Rosario Oliva
title	Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation
title_short	Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation
title_full	Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation
title_fullStr	Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation
title_full_unstemmed	Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation
title_sort	unraveling the binding characteristics of small ligands to telomeric dna by pressure modulation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/94c9a90a87ed4256a5459e738bc7c9de
work_keys_str_mv	AT rosariooliva unravelingthebindingcharacteristicsofsmallligandstotelomericdnabypressuremodulation AT sanjibmukherjee unravelingthebindingcharacteristicsofsmallligandstotelomericdnabypressuremodulation AT rolandwinter unravelingthebindingcharacteristicsofsmallligandstotelomericdnabypressuremodulation
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Unraveling the binding characteristics of small ligands to telomeric DNA by pressure modulation

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