Résumé
In bacteria, the major route of protein translocation across the cytoplasmic membrane is the so-called “Sec-pathway”. Secretory proteins that use this route are synthesized as precursors (preproteins) with an amino-terminal extension, the signal peptide. The signal peptide consists of three domains: a positively charged N-terminus (N-domain), a hydrophobic central region (H-domain) and a C-terminal domain containing the signal peptidase cleavage site. The signal peptide directs the preprotein to the translocation machinery and is needed for initiation of the translocation process. It also slows down the folding of the mature domain of a secretory preprotein, and thereby increases the time window for molecular chaperones like SecB to interact. SecB is a molecular chaperone that stabilizes preproteins in a translocation-competent (non-aggregated, loosely folded) state and that targets them to the membrane (Fig. 1, route b) (reviewed by Fekkes and Driessen, 1999). Preproteins with a very hydrophobic signal peptide and most membrane proteins are targeted to the cytoplasmic (inner) membrane via the signal recognition particle (SRP)-pathway (Fig. 1, route c). SRP binds to the H-domain of the signal peptide when it emerges from the ribosome, and subsequently targets the ribosome-bound nascent chain complex via the SRP receptor FtsY at the membrane to the translocation machinery. Preprotein translocation is mediated by a multicomponent membrane complex that consists of the membrane-associated ATPase SecA, and a large integral membrane domain consisting of SecY, SecE, SecG, SecD, SecF and YajC as separate subunits.