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A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry

Integral membrane proteins (IMPs) control countless fundamental biological processes and constitute the majority of drug targets. For this reason, uncovering their molecular mechanism of action has long been an intense field of research. They are, however, notoriously difficult to work with, mainly...

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Detalles Bibliográficos
Autores principales: Martens, Chloe, Politis, Argyris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255514/
https://www.ncbi.nlm.nih.gov/pubmed/32170968
http://dx.doi.org/10.1002/pro.3853
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author Martens, Chloe
Politis, Argyris
author_facet Martens, Chloe
Politis, Argyris
author_sort Martens, Chloe
collection PubMed
description Integral membrane proteins (IMPs) control countless fundamental biological processes and constitute the majority of drug targets. For this reason, uncovering their molecular mechanism of action has long been an intense field of research. They are, however, notoriously difficult to work with, mainly due to their localization within the heterogeneous of environment of the biological membrane and the instability once extracted from the lipid bilayer. High‐resolution structures have unveiled many mechanistic aspects of IMPs but also revealed that the elucidation of static pictures has limitations. Hydrogen–deuterium exchange coupled to mass spectrometry (HDX‐MS) has recently emerged as a powerful biophysical tool for interrogating the conformational dynamics of proteins and their interactions with ligands. Its versatility has proven particularly useful to reveal mechanistic aspects of challenging classes of proteins such as IMPs. This review recapitulates the accomplishments of HDX‐MS as it has matured into an essential tool for membrane protein structural biologists.
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spelling pubmed-72555142020-06-01 A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry Martens, Chloe Politis, Argyris Protein Sci Reviews Integral membrane proteins (IMPs) control countless fundamental biological processes and constitute the majority of drug targets. For this reason, uncovering their molecular mechanism of action has long been an intense field of research. They are, however, notoriously difficult to work with, mainly due to their localization within the heterogeneous of environment of the biological membrane and the instability once extracted from the lipid bilayer. High‐resolution structures have unveiled many mechanistic aspects of IMPs but also revealed that the elucidation of static pictures has limitations. Hydrogen–deuterium exchange coupled to mass spectrometry (HDX‐MS) has recently emerged as a powerful biophysical tool for interrogating the conformational dynamics of proteins and their interactions with ligands. Its versatility has proven particularly useful to reveal mechanistic aspects of challenging classes of proteins such as IMPs. This review recapitulates the accomplishments of HDX‐MS as it has matured into an essential tool for membrane protein structural biologists. John Wiley & Sons, Inc. 2020-03-25 2020-06 /pmc/articles/PMC7255514/ /pubmed/32170968 http://dx.doi.org/10.1002/pro.3853 Text en © 2020 The Authors. Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Martens, Chloe
Politis, Argyris
A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
title A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
title_full A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
title_fullStr A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
title_full_unstemmed A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
title_short A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
title_sort glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255514/
https://www.ncbi.nlm.nih.gov/pubmed/32170968
http://dx.doi.org/10.1002/pro.3853
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