Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?
Bottom Line: Consequently, mechanistic details and structural information about membrane protein folding are now emerging at an ever increasing pace.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: Crystallisation of SurA revealed a four-domain protein with two PPIase domains (P1 and P2) sandwiched between the N- and C-terminal domains (Fig. 5a) . PPIase domain P1 is packed against the core structure of the N- and C-terminal domains and does not show significant activity, while the more active P2 domain extends away from the core structure [77,80,81]. The PPIase activity of P2 has been shown to be increased in the presence of the adjacent chaperone domain, presumably as this domain facilitates substrate binding close to the active site of P2 . Deletion of both PPIase domains, however, did not cause a significant loss of SurA function in vivo and the isolated PPIase domains failed to complement activity in surA deletion mutants . This led to the conclusion that SurA functions mainly as a chaperone . Interestingly, mutations which would be expected to cause a loss of PPIase function in the P1 domain, if this domain were active, destabilised SurA in vitro but increased chaperone activity in vivo. This result suggests a regulatory function of the P1 domain, explaining its lack of significant PPIase activity .
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.