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

McMorran LM, Brockwell DJ, Radford SE - Arch. Biochem. Biophys. (2014)

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.

View Article: PubMed Central - PubMed

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.

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Schematic of the current model of biogenesis and chaperoning of OMPs in E. coli. (a) OMPs are synthesised on the ribosome before post-translational translocation across the inner membrane by the SecYEG translocon. Unfolded OMPs are then chaperoned across the periplasm to the β-barrel assembly machinery (BAM) complex, which aids folding and insertion into the OM. BAM complex proteins are labelled A–E, and the periplasmic polypeptide transport-associated (POTRA) domains of BamA are labelled P1-5. Horizontal black lines indicate the approximate position of the inner and outer membranes. (b) Flow diagram of the periplasmic and outer membrane-anchored proteins which may be implicated in OMP biogenesis. (a) was adapted from [92] with permission from Elsevier, © 2013, while (b) was reproduced from [73] with permission from John Wiley and Sons, © 2005.
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f0020: Schematic of the current model of biogenesis and chaperoning of OMPs in E. coli. (a) OMPs are synthesised on the ribosome before post-translational translocation across the inner membrane by the SecYEG translocon. Unfolded OMPs are then chaperoned across the periplasm to the β-barrel assembly machinery (BAM) complex, which aids folding and insertion into the OM. BAM complex proteins are labelled A–E, and the periplasmic polypeptide transport-associated (POTRA) domains of BamA are labelled P1-5. Horizontal black lines indicate the approximate position of the inner and outer membranes. (b) Flow diagram of the periplasmic and outer membrane-anchored proteins which may be implicated in OMP biogenesis. (a) was adapted from [92] with permission from Elsevier, © 2013, while (b) was reproduced from [73] with permission from John Wiley and Sons, © 2005.

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 [73]. 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 [73]. 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) [73].


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

McMorran LM, Brockwell DJ, Radford SE - Arch. Biochem. Biophys. (2014)

Schematic of the current model of biogenesis and chaperoning of OMPs in E. coli. (a) OMPs are synthesised on the ribosome before post-translational translocation across the inner membrane by the SecYEG translocon. Unfolded OMPs are then chaperoned across the periplasm to the β-barrel assembly machinery (BAM) complex, which aids folding and insertion into the OM. BAM complex proteins are labelled A–E, and the periplasmic polypeptide transport-associated (POTRA) domains of BamA are labelled P1-5. Horizontal black lines indicate the approximate position of the inner and outer membranes. (b) Flow diagram of the periplasmic and outer membrane-anchored proteins which may be implicated in OMP biogenesis. (a) was adapted from [92] with permission from Elsevier, © 2013, while (b) was reproduced from [73] with permission from John Wiley and Sons, © 2005.
© Copyright Policy
Related In: Results  -  Collection

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f0020: Schematic of the current model of biogenesis and chaperoning of OMPs in E. coli. (a) OMPs are synthesised on the ribosome before post-translational translocation across the inner membrane by the SecYEG translocon. Unfolded OMPs are then chaperoned across the periplasm to the β-barrel assembly machinery (BAM) complex, which aids folding and insertion into the OM. BAM complex proteins are labelled A–E, and the periplasmic polypeptide transport-associated (POTRA) domains of BamA are labelled P1-5. Horizontal black lines indicate the approximate position of the inner and outer membranes. (b) Flow diagram of the periplasmic and outer membrane-anchored proteins which may be implicated in OMP biogenesis. (a) was adapted from [92] with permission from Elsevier, © 2013, while (b) was reproduced from [73] with permission from John Wiley and Sons, © 2005.
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 [73]. 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 [73]. 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) [73].

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.

View Article: PubMed Central - PubMed

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
Related in: MedlinePlus