A glimpse into the molecular mechanism of integral membrane proteins through hydrogen–deuterium exchange mass spectrometry
Open Access
- 25 March 2020
- journal article
- review article
- Published by Wiley in Protein Science
- Vol. 29 (6), 1285-1301
- https://doi.org/10.1002/pro.3853
Abstract
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.Keywords
This publication has 84 references indexed in Scilit:
- Dynamics of a bacterial multidrug ABC transporter in the inward- and outward-facing conformationsProceedings of the National Academy of Sciences of the United States of America, 2012
- X-ray structures of LeuT in substrate-free outward-open and apo inward-open statesNature, 2012
- Ligand-Dependent Perturbation of the Conformational Ensemble for the GPCR β2 Adrenergic Receptor Revealed by HDXStructure, 2011
- Conformational changes in the G protein Gs induced by the β2 adrenergic receptorNature, 2011
- False EX1 signatures caused by sample carryover during HX MS analysesInternational Journal of Mass Spectrometry, 2011
- The Norrin/Frizzled4 signaling pathway in retinal vascular development and diseaseTrends in Molecular Medicine, 2010
- Conformational Analysis of Membrane Proteins in Phospholipid Bilayer Nanodiscs by Hydrogen Exchange Mass SpectrometryAnalytical Chemistry, 2010
- Dynamics of the β2-Adrenergic G-Protein Coupled Receptor Revealed by Hydrogen−Deuterium ExchangeAnalytical Chemistry, 2010
- Analysis of Protein Conformation and Dynamics by Hydrogen/Deuterium Exchange MSAnalytical Chemistry, 2009
- Mapping protein dynamics in catalytic intermediates of the redox-driven proton pump cytochrome c oxidaseProceedings of the National Academy of Sciences of the United States of America, 2006