Trigger factor is a bona fide secretory pathway chaperone that interacts with SecB and the translocase

Abstract Bacterial secretory preproteins are translocated across the inner membrane post‐translationally by the Sec YEG ‐SecA translocase. Mature domain features and signal peptides maintain preproteins in kinetically trapped, largely soluble, folding intermediates. Some aggregation‐prone preproteins require chaperones, like trigger factor ( TF ) and SecB, for solubility and/or targeting. TF antagonizes the contribution of SecB to secretion by an unknown molecular mechanism. We reconstituted this interaction in vitro and studied targeting and secretion of the model preprotein pro‐OmpA. TF and SecB display distinct, unsuspected roles in secretion. Tightly associating TF :pro‐OmpA targets the translocase at SecA, but TF prevents pro‐OmpA secretion. In solution, SecB binds TF :pro‐OmpA with high affinity. At the membrane, when bound to the SecA C‐tail, SecB increases TF and TF :pro‐OmpA affinities for the translocase and allows pro‐OmpA to resume translocation. Our data reveal that TF , a main cytoplasmic folding pathway chaperone, is also a bona fide post‐translational secretory chaperone that directly interacts with both SecB and the translocase to mediate regulated protein secretion. Thus, TF links the cytoplasmic folding and secretion chaperone networks.