Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?
Bottom Line: 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.
Affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK; School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.Show MeSH
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Mentions: Following their synthesis in the cytosol, OMPs are targeted to the SecYEG translocon by the SecB chaperone, whereupon they are translocated across the IM through SecYEG in an unfolded state [71,72]. The unfolded OMPs must be protected from aggregation and must be able to traverse the periplasm, including the peptidoglycan layer, and then correctly fold and insert into the OM . These requirements suggest that transport across the periplasm and membrane insertion may be facilitated processes and, indeed, a number of periplasmic and OM-associated proteins have been implicated in the OMP assembly pathway . These proteins can be roughly grouped into three categories: proteases; chaperones which stabilise unfolded and non-native conformations of their client proteins; and folding catalysts, which catalyse rate-limiting steps in folding (Fig. 4a and b) .
Affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK; School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.