Hydrogen/deuterium exchange-mass spectrometry of integral membrane proteins in native-like environments: current scenario and the way forward. Issue 2 (29th March 2023)

• Record Type: Journal Article
• Authors: Javed, Waqas; Griffiths, Damon; Politis, Argyris
• Editors: Britt, Hannah; Beveridge, Rebecca; Calabrese, Antonio
• Is Part Of: Essays in biochemistry. Volume 67:Issue 2(2023)
• Page Start: 187
• Page End: 200
• Publication Date: 2023-03-29
• Subjects: hydrogen-deuterium exchange mass spectrometry -- liposomes -- membrane proteins -- membrane vesicles -- nanodiscs; Biochemistry -- Periodicals; 572
• DOI: 10.1042/EBC20220173
• Languages: English
• ISSNs: 0071-1365

Abstract

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 have the potential to perturbate their structure and dynamics. To circumnavigate this issue, an array of membrane mimetics has been developed that 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 the present 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 that are likely to play a significant role in the generation of high-quality HDX-MS data of IMPs in the future.