Protease-deficient DegP suppresses lethal effects of a mutant OmpC protein by its capture

The expression of assembly-defective outer membrane proteins can confer lethality if they are not degraded by envelope proteases. We report here that the expression of a mutant OmpC protein, OmpC_2cys which forms disulfide bonds in the periplasm due to the presence of two non-native cysteine residues, is lethal in cells lacking the major periplasmic protease, DegP. This lethality is not observed in dsbA strains that have diminished ability to form periplasmic disulfide bonds. Our data show that this OmpC_2Cys mediated lethality in a degP:: Km^r dsbA⁺ background can be reversed by a DegP variant, DegP_S210A, that is devoid of its proteolytic activity but retains its reported chaperone activity. However, DegP_S210A does not reverse the lethal effect of OmpC_2Cys, by correcting its assembly but rather by capturing misfolded mutant OmpC polypeptides and thus removing them from the assembly pathway. Displacement of OmpC_2Cys by DegP_S210A also alleviates the negative effect that the mutant OmpC protein has on wild-type OmpF.