Subtilisin-like autotransporter serves as maturation protease in a bacterial secretion pathway

Proteins of Gram-negative bacteria destined to the extracellular milieu mus t cross the two cellular membranes and then fold at the appropriate time an d place. The synthesis of a precursor may be a strategy to maintain secreti on competence while preventing aggregation or premature folding (especially for large proteins). The secretion of 230 kDa filamentous haemagglutinin ( FHA) of Bordetella pertussis requires the synthesis and the maturation of a 367 kDa precursor that undergoes the proteolytic removal of its similar to 130 kDa C-terminal intramolecular chaperone domain. We have identified a s pecific protease, SphB1, responsible for the timely maturation of the precu rsor FhaB, which allows for extracellular release of FHA. SphB1 is a large exported protein with a subtilisin-like domain and a C-terminal domain typi cal of bacterial autotransporters. SphB1 is the first described subtilisin- like protein that serves as a specialized maturation protease in a secretio n pathway of Gram-negative bacteria. This is reminiscent of pro-protein con vertases of eukaryotic cells.