The lipid environment of Escherichia coli Aquaporin Z

Biochim Biophys Acta Biomembr. 2019 Feb 1;1861(2):431-440. doi: 10.1016/j.bbamem.2018.10.017. Epub 2018 Nov 8.


In this study, we have investigated the lipids surrounding AqpZ, and the effects of a destabilizing mutation W14A (Schmidt and Sturgis, 2017) on lipid protein interactions. In a first approach, we used Styrene Maleic Acid copolymer to prepare AqpZ containing nanodiscs, and these were analyzed for their lipid content, investigating both the lipid head-group and acyl-chain compositions. These results were complemented by native mass spectrometry of purified AqpZ in the presence of lipids, to give insights of variations in lipid binding at the surface of AqpZ. In an effort to gain molecular insights, to aid interpretation of these results, we performed a series of coarse grained molecular dynamics simulations of AqpZ, in mixed lipid membranes, and correlated our observations with the experimental measurements. These various results are then integrated to give a clearer picture of the lipid environment of AqpZ, both in the native membrane, and in lipid nanodiscs. We conclude that AqpZ contains a lipid binding-site, at the interface between the monomers of the tetramer, that is specific for cardiolipin. Almost all the cardiolipin, in AqpZ containing nanodiscs, is probably associated with this site. The SMA 3:1 nanodiscs we obtained contain a rather high proportion of lipid, and in the case of nanodiscs containing AqpZ cardiolipin is depleted. This is possibly because, in the membrane, there is little cardiolipin not associated with binding sites on the surface of the different membrane proteins. Surprisingly, we see no evidence for lipid sorting based on acyl chain length, even in the presence of a large hydrophobic mismatch, suggesting that conformational restrictions are energetically less costly than lipid sorting.

Keywords: Cardiolipin; Lipidomics; Membrane protein; SMALP; Styrene maleic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporins / metabolism*
  • Cell Membrane / metabolism
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism*
  • Lipids / chemistry*
  • Lipids / isolation & purification
  • Molecular Dynamics Simulation
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Phospholipids / isolation & purification


  • Aquaporins
  • Escherichia coli Proteins
  • Lipids
  • Phospholipids
  • aqpZ protein, E coli