Folding of β-barrel membrane proteins in lipid bilayers - Unassisted and assisted folding and insertion

Biochim Biophys Acta. 2015 Sep;1848(9):1927-43. doi: 10.1016/j.bbamem.2015.05.004. Epub 2015 May 14.


In cells, β-barrel membrane proteins are transported in unfolded form to an outer membrane into which they fold and insert. Model systems have been established to investigate the mechanisms of insertion and folding of these versatile proteins into detergent micelles, lipid bilayers and even synthetic amphipathic polymers. In these experiments, insertion into lipid membranes is initiated from unfolded forms that do not display residual β-sheet secondary structure. These studies therefore have allowed the investigation of membrane protein folding and insertion in great detail. Folding of β-barrel membrane proteins into lipid bilayers has been monitored from unfolded forms by dilution of chaotropic denaturants that keep the protein unfolded as well as from unfolded forms present in complexes with molecular chaperones from cells. This review is aimed to provide an overview of the principles and mechanisms observed for the folding of β-barrel transmembrane proteins into lipid bilayers, the importance of lipid-protein interactions and the function of molecular chaperones and folding assistants. This article is part of a Special Issue entitled: Lipid-protein interactions.

Keywords: BAM complex; Kinetics; Membrane protein folding; OmpA; Outer membrane; Periplasmic chaperone; β-barrel membrane protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Kinetics
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Models, Biological
  • Models, Molecular
  • Protein Folding*
  • Protein Structure, Secondary*


  • Bacterial Proteins
  • Lipid Bilayers
  • Membrane Proteins