Hydrogen/Deuterium Exchange-Mass Spectrometry of Integral Membrane Proteins in Native-like Environments: Current Scenario and the Way forward

Waqas Javed, Damon Griffiths, Anargyros Politis

Research output: Contribution to journalArticlepeer-review

Abstract

Integral membrane proteins (IMPs) perform a range of diverse functions and their dysfunction underlies numerous pathological conditions. Consequently, IMPs constitute most drug targets, and the elucidation of their mechanism of action has become an intense field of research. Historically, IMP studies have relied on their extraction from membranes using detergents, which has the potential to perturbate their structure and dynamics. To circumnavigate this issue, an array of membrane mimetics has been developed which aim to reconstitute IMPs into native-like lipid environments that more accurately represent the biological membrane. Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has emerged as a versatile tool for probing protein dynamics in solution. The continued development of HDX-MS methodology has allowed practitioners to investigate IMPs using increasingly native-like membrane mimetics, and even pushing the study of IMPs into the in vivo cellular environment. Consequently, HDX-MS has come of age and is playing an ever-increasingly important role in the IMP structural biologist toolkit. In this mini review, we discuss the evolution of membrane mimetics in the HDX-MS context, focusing on seminal publications and recent innovations that have led to this point. We also discuss state-of-the-art methodological and instrumental advancements which are likely to play a significant role in the generation of high quality HDX-MS data of IMPs in the future.
Original languageEnglish
Pages (from-to)187–200
JournalEssays in Biochemistry
Volume67
Issue number2
DOIs
Publication statusPublished - 29 Mar 2024

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