The synthesis of export-defective proteins can interfere with normal protein export in Escherichia coli.

We have analyzed the kinetics of maturation for certain bacterial envelope proteins in Escherichia coli strains that are also concomitantly producing an export-defective protein. Our data indicate that proteins with defective signal peptides, rendered nonfunctional by either point mutation or deletion, interfere with the normal export of other envelope proteins. Expression of interference requires that the interfering protein: (i) exhibit a major export defect; (ii) be synthesized at a high rate; and (iii) be actively synthesized at the time interference is being measured. The latter data suggest that interference is a cotranslational process. Intragenic or extragenic suppression of the export defect exhibited by the interfering protein relieves interference in a manner that is directly related to strength of suppression. These and additional data suggest that interference occurs at a very early step in the secretory process. We interpret these results to indicate that proteins with defective signal peptides are still recognized as proteins destined for secretion and are, therefore, at least transiently incorporated into the cell's secretory pathway. The incorporation of an export-defective protein into the secretory pathway disrupts the normal protein traffic from the cytoplasm to the various extracellular compartments.