A large amount of the human proteome is composed of highly dynamic regions that do not adopt a single static conformation. These regions are defined as intrinsically disordered, and they are found in a third of all eukaryotic proteins. They play instrumental roles in many aspects of protein signaling, but can be challenging to characterize by biophysical methods. Intriguingly, many of these regions can adopt stable secondary structure upon interaction with a variety of binding partners, including proteins, lipids, and ligands. This review will discuss the application of Hydrogen-deuterium exchange mass spectrometry (HDX-MS) as a powerful biophysical tool that is particularly well suited for structural and functional characterization of intrinsically disordered regions in proteins. A focus will be on the theory of hydrogen exchange, and its practical application to identify disordered regions, as well as characterize how they participate in protein–protein and protein–membrane interfaces. A particular emphasis will be on how HDX-MS data can be presented specifically tailored for analysis of intrinsically disordered regions, as well as the technical aspects that are critical to consider when designing HDX-MS experiments for proteins containing intrinsically disordered regions.
Many dietary plants possess high levels of 18-carbon containing lipids from both omega-6 and omega-3 unsaturated fatty acids (e.g., linoleic and alpha-linolenic acid, respectively). These dietary lipids can be metabolized to lipid mediators collectively termed octadecanoids, which can in turn interact with immune cells (e.g., macrophages, eosinophils) to exert a number of potent biological effects. These octadecanoid lipid mediators have been little studied and represent an exciting new area of lipid biochemistry. For further information, see the review in this issue by Quaranta and colleagues (pages 1569–1582). Cover image credit: Emmanuelle Chevallier.
Investigating how intrinsically disordered regions contribute to protein function using HDX-MS
Matthew A.H. Parson, Meredith L. Jenkins, John E. Burke; Investigating how intrinsically disordered regions contribute to protein function using HDX-MS. Biochem Soc Trans 16 December 2022; 50 (6): 1607–1617. doi: https://doi.org/10.1042/BST20220206
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