Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution

Abstract Hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (HDXMS) is a rapid and effective method for localizing and determining protein stability and dynamics. Localization is routinely limited to a peptide resolution of 5 to 20 amino acid residues. HDXMS data can contain informatio...

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Autores principales:	Chris Gessner, Wieland Steinchen, Sabrina Bédard, John J. Skinner, Virgil L. Woods, Thomas J. Walsh, Gert Bange, Dionysios P. Pantazatos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a71050ed12c6431e8c2981c692e1ae08
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spelling	oai:doaj.org-article:a71050ed12c6431e8c2981c692e1ae082021-12-02T15:05:08ZComputational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution10.1038/s41598-017-03922-32045-2322https://doaj.org/article/a71050ed12c6431e8c2981c692e1ae082017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03922-3https://doaj.org/toc/2045-2322Abstract Hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (HDXMS) is a rapid and effective method for localizing and determining protein stability and dynamics. Localization is routinely limited to a peptide resolution of 5 to 20 amino acid residues. HDXMS data can contain information beyond that needed for defining protein stability at single amide resolution. Here we present a method for extracting this information from an HDX dataset to generate a HDXMS protein stability fingerprint. High resolution (HR)-HDXMS was applied to the analysis of a model protein of a spectrin tandem repeat that exemplified an intuitive stability profile based on the linkage of two triple helical repeats connected by a helical linker. The fingerprint recapitulated expected stability maximums and minimums with interesting structural features that corroborate proposed mechanisms of spectrin flexibility and elasticity. HR-HDXMS provides the unprecedented ability to accurately assess protein stability at the resolution of a single amino acid. The determination of HDX stability fingerprints may be broadly applicable in many applications for understanding protein structure and function as well as protein ligand interactions.Chris GessnerWieland SteinchenSabrina BédardJohn J. SkinnerVirgil L. WoodsThomas J. WalshGert BangeDionysios P. PantazatosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chris Gessner Wieland Steinchen Sabrina Bédard John J. Skinner Virgil L. Woods Thomas J. Walsh Gert Bange Dionysios P. Pantazatos Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution
description	Abstract Hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (HDXMS) is a rapid and effective method for localizing and determining protein stability and dynamics. Localization is routinely limited to a peptide resolution of 5 to 20 amino acid residues. HDXMS data can contain information beyond that needed for defining protein stability at single amide resolution. Here we present a method for extracting this information from an HDX dataset to generate a HDXMS protein stability fingerprint. High resolution (HR)-HDXMS was applied to the analysis of a model protein of a spectrin tandem repeat that exemplified an intuitive stability profile based on the linkage of two triple helical repeats connected by a helical linker. The fingerprint recapitulated expected stability maximums and minimums with interesting structural features that corroborate proposed mechanisms of spectrin flexibility and elasticity. HR-HDXMS provides the unprecedented ability to accurately assess protein stability at the resolution of a single amino acid. The determination of HDX stability fingerprints may be broadly applicable in many applications for understanding protein structure and function as well as protein ligand interactions.
format	article
author	Chris Gessner Wieland Steinchen Sabrina Bédard John J. Skinner Virgil L. Woods Thomas J. Walsh Gert Bange Dionysios P. Pantazatos
author_facet	Chris Gessner Wieland Steinchen Sabrina Bédard John J. Skinner Virgil L. Woods Thomas J. Walsh Gert Bange Dionysios P. Pantazatos
author_sort	Chris Gessner
title	Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution
title_short	Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution
title_full	Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution
title_fullStr	Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution
title_full_unstemmed	Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution
title_sort	computational method allowing hydrogen-deuterium exchange mass spectrometry at single amide resolution
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a71050ed12c6431e8c2981c692e1ae08
work_keys_str_mv	AT chrisgessner computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution AT wielandsteinchen computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution AT sabrinabedard computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution AT johnjskinner computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution AT virgillwoods computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution AT thomasjwalsh computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution AT gertbange computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution AT dionysiosppantazatos computationalmethodallowinghydrogendeuteriumexchangemassspectrometryatsingleamideresolution
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Computational method allowing Hydrogen-Deuterium Exchange Mass Spectrometry at single amide Resolution

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