A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export

Abstract

Summary: Lantibiotic and non‐lantibiotic bacteriocins are synthesized as precursor peptides containing N‐terminal extensions (leader peptides) which are cleaved off during maturation. Most non‐lantibiotics and also some lantibiotics have leader peptides of the so‐ called double‐glycine type. These leader peptides share consensus sequences and also a common processing site with two conserved glycine residues In positions ‐1 and 2. The double‐glycine‐type leader peptides are unrelated to the N‐terminal signal sequences which direct proteins across the cytoplasmic membrane via the sec pathway. Their processing sites are also different from typical signal peptidase cleavage sites, suggesting that a different processing enzyme is involved. Peptide bacteriocins are exported across the cytoplasmic membrane by a dedicated ATP‐binding cassette (ABC) transporter. Here we show that the ABC transporter is the maturation protease and that its proteolytic domain resides in the N‐terminal part of the protein. This result demonstrates that the ABC transporter has a dual function: (i) removal of the leader peptide from its substrate, and (ii) translocation of its substrate across the cytoplasmic membrane. This represents a novel strategy for secretion of bacterial proteins.