Direct protein-lipid interactions shape the conformational landscape of secondary transporters

Nat Commun. 2018 Oct 8;9(1):4151. doi: 10.1038/s41467-018-06704-1.


Secondary transporters undergo structural rearrangements to catalyze substrate translocation across the cell membrane - yet how such conformational changes happen within a lipid environment remains poorly understood. Here, we combine hydrogen-deuterium exchange mass spectrometry (HDX-MS) with molecular dynamics (MD) simulations to understand how lipids regulate the conformational dynamics of secondary transporters at the molecular level. Using the homologous transporters XylE, LacY and GlpT from Escherichia coli as model systems, we discover that conserved networks of charged residues act as molecular switches that drive the conformational transition between different states. We reveal that these molecular switches are regulated by interactions with surrounding phospholipids and show that phosphatidylethanolamine interferes with the formation of the conserved networks and favors an inward-facing state. Overall, this work provides insights into the importance of lipids in shaping the conformational landscape of an important class of transporters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism
  • Deuterium Exchange Measurement
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Mass Spectrometry
  • Membrane Lipids / chemistry*
  • Membrane Lipids / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism
  • Molecular Dynamics Simulation
  • Monosaccharide Transport Proteins / chemistry
  • Monosaccharide Transport Proteins / metabolism
  • Protein Binding
  • Protein Conformation*
  • Symporters / chemistry
  • Symporters / metabolism


  • Escherichia coli Proteins
  • GlpT protein, E coli
  • LacY protein, E coli
  • Membrane Lipids
  • Membrane Proteins
  • Membrane Transport Proteins
  • Monosaccharide Transport Proteins
  • Symporters
  • xylE protein, E coli