Structural predictions of the functions of membrane proteins from HDX-MS

Biochem Soc Trans. 2020 Jun 30;48(3):971-979. doi: 10.1042/BST20190880.

Abstract

HDX-MS has emerged as a powerful tool to interrogate the structure and dynamics of proteins and their complexes. Recent advances in the methodology and instrumentation have enabled the application of HDX-MS to membrane proteins. Such targets are challenging to investigate with conventional strategies. Developing new tools are therefore pertinent for improving our fundamental knowledge of how membrane proteins function in the cell. Importantly, investigating this central class of biomolecules within their native lipid environment remains a challenge but also a key goal ahead. In this short review, we outline recent progresses in dissecting the conformational mechanisms of membrane proteins using HDX-MS. We further describe how the use of computational strategies can aid the interpretation of experimental data and enable visualisation of otherwise intractable membrane protein states. This unique integration of experiments with computations holds significant potential for future applications.

Keywords: hydrogen-deuterium exchange mass spectrometry; integrative modelling; membrane proteins; transport.

Publication types

  • Review

MeSH terms

  • Hydrogen Deuterium Exchange-Mass Spectrometry / methods*
  • Lipids / chemistry
  • Membrane Proteins / chemistry*
  • Protein Conformation

Substances

  • Lipids
  • Membrane Proteins