Figure 1

Schematic representation of folding pathways and cellular localization of proteins that depend on oxidative environment to reach their native structure. Unfolded proteins can be translocated into the periplasm post-translationally (Sec mechanism) or co-translationally (SPR mechanism), according to their specific leader sequences. SecB is the physiological chaperone involved in stabilizing unfolded proteins bound to Sec translocation machinery, but the activity of other cytoplasmic chaperones like DnaK can be beneficial. Once in the periplasm proteins folding is mediated by the Dsb oxidases/isomerases, by chaperones such as Skp, DegP and FkpA, and by peptidyl-prolyl isomerases such as SurA, PpiA, and PpiB. Double mutant strains, in which the thioredoxin/glutaredoxin reductase (trxB^-, gor^-) pathway is silenced, are characterized by the presence of an oxidizing cytoplasm, compatible with the folding of proteins that need disulfide bridges for stabilizing their structure. Cytoplasmic accumulation of correctly folded disulfide-dependent proteins is improved by disulfide isomerase DsbC co-expression and cytoplasmic chaperone (DnaKJE, GroELS, ClpB). Finally, proteins provided with a Tat export leader sequence first fold in the cytoplasm and then are tanslocated into the periplasm. Chaperones like DnaKJE, can stabilize the precursor in the cytoplasm and chaperones such as SlyD and TorD support the pathway efficiency probably binding to the export leader peptide.