The targeting pathway of Escherichia coli presecretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal

Previous studies have demonstrated that presecretory proteins such as malto se binding protein (MBP) and outer membrane protein A (OmpA) are targeted t o the Escherichia coil inner membrane by the molecular chaperone SecB, but that integral membrane proteins are targeted by the signal recognition part icle (SRP). In vitro studies have suggested that trigger factor binds to a sequence near the N terminus of the mature region of OmpA and shunts the pr otein into the SecB pathway by blocking an interaction between SRP and the signal peptide. By contrast, we have found that the targeting pathway of a protein under physiological conditions is dictated by the composition of it s targeting signal. Replacement of the MBP or OmpA signal peptide with the first transmembrane segment of AcrB abolished the dependence on SecB for tr ansport and rerouted both proteins into the SRP targeting pathway. More mod est alterations of the MBP signal peptide that simply increase its hydropho bicity also promoted SRP binding. Furthermore, we obtained evidence that SR P has a low affinity for typical signal peptides in vivo. These results imp ly that different classes of E. coli proteins are targeted by distinct path ways because bacterial SRP binds to a more restricted range of targeting si gnals than its eukaryotic counterpart.