Bacterial leader peptidase, a membrane protein without a leader peptide, uses the same export pathway as pre-secretory proteins.

Leader peptidase typifies a group of proteins of the plasma membrane of E. coli which span the membrane and are synthesized without a cleaved amino-terminal leader (signal) sequence. The membrane assembly properties of these proteins have not been previously reported. We find that the membrane electrochemical potential is necessary for the insertion of a large domain of leader peptidase across the membrane. In the absence of potential, the peptidase accumulates inside the cell in tight association with the plasma membrane. Upon restoration of the potential, accumulated peptidase inserts across the membrane, indicating that this insertion is not mechanistically coupled to polypeptide chain growth. The normal, trans-bilayer peptidase and that which accumulates in the absence of potential have different conformations, as shown by the relative resistance of the trans-bilayer enzyme to digestion by trypsin or chymotrypsin in cell lysates. Membrane insertion is accompanied by this conformational change. This assembly reaction has several features predicted by the hypothesis of membrane-triggered folding.