Interrogating Membrane Protein Conformational Dynamics within Native Lipid Compositions

Angew Chem Int Ed Engl. 2017 Dec 4;56(49):15654-15657. doi: 10.1002/anie.201709657. Epub 2017 Nov 8.


The interplay between membrane proteins and the lipids of the membrane is important for cellular function, however, tools enabling the interrogation of protein dynamics within native lipid environments are scarce and often invasive. We show that the styrene-maleic acid lipid particle (SMALP) technology can be coupled with hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate membrane protein conformational dynamics within native lipid bilayers. We demonstrate changes in accessibility and dynamics of the rhomboid protease GlpG, captured within three different native lipid compositions, and identify protein regions sensitive to changes in the native lipid environment. Our results illuminate the value of this approach for distinguishing the putative role(s) of the native lipid composition in modulating membrane protein conformational dynamics.

Keywords: lipids; mass spectrometry; membrane nanodiscs; membrane proteins; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / metabolism
  • Deuterium Exchange Measurement
  • Endopeptidases / metabolism
  • Escherichia coli Proteins / metabolism
  • Lipids / chemistry*
  • Mass Spectrometry
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Protein Conformation


  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • GlpG protein, E coli
  • Lipids
  • Membrane Proteins
  • Endopeptidases