Hydrogen/Deuterium Exchange Mass Spectrometry: Fundamentals, Limitations, and Opportunities.

Autor: Konermann L; Department of Chemistry, The University of Western Ontario, London, Ontario, Canada. Electronic address: konerman@uwo.ca., Scrosati PM; Department of Chemistry, The University of Western Ontario, London, Ontario, Canada.
Jazyk: angličtina
Zdroj: Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2024 Nov; Vol. 23 (11), pp. 100853. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1016/j.mcpro.2024.100853
Abstrakt: Hydrogen/deuterium exchange mass spectrometry (HDX-MS) probes dynamic motions of proteins by monitoring the kinetics of backbone amide deuteration. Dynamic regions exhibit rapid HDX, while rigid segments are more protected. Current data readouts focus on qualitative comparative observations (such as "residues X to Y become more protected after protein exposure to ligand Z"). At present, it is not possible to decode HDX protection patterns in an atomistic fashion. In other words, the exact range of protein motions under a given set of conditions cannot be uncovered, leaving space for speculative interpretations. Amide back exchange is an under-appreciated problem, as the widely used (m-m 0 )/(m 100 -m 0 ) correction method can distort HDX kinetic profiles. Future data analysis strategies require a better fundamental understanding of HDX events, going beyond the classical Linderstrøm-Lang model. Combined with experiments that offer enhanced spatial resolution and suppressed back exchange, it should become possible to uncover the exact range of motions exhibited by a protein under a given set of conditions. Such advances would provide a greatly improved understanding of protein behavior in health and disease.
Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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