Two distinct forms of peptidylprolyl-cis-trans-isomerase are expressed separately in periplasmic and cytoplasmic compartments of Escherichia coli cells.

Peptidylprolyl-cis-trans-isomerase (PPIase) is thought to be essential for protein folding in the cell. Two forms, a and b, of PPIase and their corresponding genes were isolated from Escherichia coli cells. Despite their insensitivity to cyclosporin A (CsA), both amino acid sequences were homologous and related to that of pig cyclophilin, a protein that has PPIase activity sensitive to CsA (Takahashi et al., 1989). PPIase a is found to be identical with the E. coli ORF 190 gene product that was sequenced by Kawamukai et al. (1989) and overexpressed by Liu and Walsh (1990). It is translocated into E. coli periplasmic space with the signal sequence. PPIase b lacks a hydrophobic amino acid stretch which could serve as a signal sequence or a transmembrane domain, and it is detected mainly in the bacterial cytoplasm. These findings indicate that proteins with the ability to assist folding of various polypeptides are located on both sides of the inner membrane. Thus, we propose that the folding of some exported proteins may be catalyzed by the periplasmic proline isomerase and, in turn, that some proteins which have isomerized may not be translocated efficiently.