Pediocin‐like antimicrobial peptides (class IIa bacteriocins) and their immunity proteins: biosynthesis, structure, and mode of action

Abstract

Pediocin‐like antimicrobial peptides (AMPs) form a group of lactic acid bacteria produced, cationic membrane‐permeabilizing peptides with 37 to 48 residues. Upon exposure to membrane‐mimicking entities, their hydrophilic, cationic, and highly conserved N‐terminal region forms a three‐stranded antiparallel β‐sheet supported by a conserved disulfide bridge. This N‐terminal β‐sheet region is followed by a central amphiphilic α‐helix and this in most (if not all) of these peptides is followed by a rather extended C‐terminal tail that folds back onto the central α‐helix, thereby creating a hairpin‐like structure in the C‐terminal half. There is a flexible hinge between the β‐sheet N‐terminal region and the hairpin C‐terminal region and one thus obtains two domains that may move relative to each other. The cationic N‐terminal β‐sheet domain mediates binding of the pediocin‐like AMPs to the target‐cell surface through electrostatic interactions, while the more hydrophobic and amphiphilic C‐terminal hairpin domain penetrates into the hydrophobic part of the target‐cell membrane, thereby mediating leakage through the membrane. The hinge provides the structural flexibility that enables the C‐terminal hairpin domain to dip into the hydrophobic part of the membrane. Despite extensive sequence similarities, these AMPs differ markedly in their target‐cell specificity, and results obtained with hybrid AMPs indicate that the membrane‐penetrating hairpin‐like C‐terminal domain is the major specificity determinant. Bacteria that produce pediocin‐like AMPs also produce a 11‐kDa cognate immunity protein that protects the producer. The immunity proteins are well‐structured, 4‐helix bundle cytosolic proteins. They show a high degree of specificity in that they largely recognize and confer immunity only to their cognate AMP and in some cases to a few AMPs that are closely related to their cognate AMP. The C‐terminal half of the immunity proteins contains a domain that is involved in specific recognition of the C‐terminal membrane‐penetrating specificity‐determining hairpin domain of the cognate AMP. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.