Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?

Arch Biochem Biophys. 2014 Dec 15;564:265-80. doi: 10.1016/ Epub 2014 Mar 5.


Research into the mechanisms by which proteins fold into their native structures has been on-going since the work of Anfinsen in the 1960s. Since that time, the folding mechanisms of small, water-soluble proteins have been well characterised. By contrast, progress in understanding the biogenesis and folding mechanisms of integral membrane proteins has lagged significantly because of the need to create a membrane mimetic environment for folding studies in vitro and the difficulties in finding suitable conditions in which reversible folding can be achieved. Improved knowledge of the factors that promote membrane protein folding and disfavour aggregation now allows studies of folding into lipid bilayers in vitro to be performed. Consequently, mechanistic details and structural information about membrane protein folding are now emerging at an ever increasing pace. Using the panoply of methods developed for studies of the folding of water-soluble proteins. This review summarises current knowledge of the mechanisms of outer membrane protein biogenesis and folding into lipid bilayers in vivo and in vitro and discusses the experimental techniques utilised to gain this information. The emerging knowledge is beginning to allow comparisons to be made between the folding of membrane proteins with current understanding of the mechanisms of folding of water-soluble proteins.

Keywords: BAM complex; Outer membrane protein; Periplasmic chaperone; Protein folding; Protein stability; Φ-Value analysis.

Publication types

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

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism*
  • Protein Folding*


  • Bacterial Outer Membrane Proteins
  • Lipid Bilayers