Structure and Mode-of-Action of the Two-Peptide (Class-IIb) Bacteriocins

Abstract

This review focuses on the structure and mode-of-action of the two-peptide (class-IIb) bacteriocins that consist of two different peptides whose genes are next to each other in the same operon. Optimal antibacterial activity requires the presence of both peptides in about equal amounts. The two peptides are synthesized as preforms that contain a 15–30 residue double-glycine-type N-terminal leader sequence that is cleaved off at the C-terminal side of two glycine residues by a dedicated ABC-transporter that concomitantly transfers the bacteriocin peptides across cell membranes. Two-peptide bacteriocins render the membrane of sensitive bacteria permeable to a selected group of ions, indicating that the bacteriocins form or induce the formation of pores that display specificity with respect to the transport of molecules. Based on structure–function studies, it has been proposed that the two peptides of two-peptide bacteriocins form a membrane-penetrating helix–helix structure involving helix–helix-interacting GxxxG-motifs that are present in all characterized two-peptide bacteriocins. It has also been suggested that the membrane-penetrating helix–helix structure interacts with an integrated membrane protein, thereby triggering a conformational alteration in the protein, which in turn causes membrane-leakage. This proposed mode-of-action is similar to the mode-of-action of the pediocin-like (class-IIa) bacteriocins and lactococcin A (a class-IId bacteriocin), which bind to a membrane-embedded part of the mannose phosphotransferase permease in a manner that causes membrane-leakage and cell death.

Defining the Structure and Receptor Binding Domain of the Leaderless Bacteriocin LsbB

“…It has been suggested that most two-peptide bacteriocins probably form a transmembrane helix-helix structure (11). In the case of the two-peptide bacteriocin lactococcin G, one of the peptides (LcnG-␣), like LsbB, contains a series of cationic residues (residues 35-39: RKKKH) at the C-terminal part.…”

“…The three-dimensional structures of only a few bacteriocins have presently been determined; these mostly include some modified bacteriocins called lantibiotics and some nonmodified bacteriocins belonging to the pediocin-like and two-peptide bacteriocin subgroups (7)(8)(9)(10)(11). Even for these bacteriocins, very little is known about the part of these peptides that is directly involved in receptor binding or pore formation (12).…”

Bacteriocins of Facultatively-Anaerobic Endosporeforming Bacteria

“…Наслідком зв'язування бактеріоцину з рецептором є перетворення комплексу «бактеріо-цин-транспортер» на трансмембранний канал, через який відбувається витік розчинних компонентів цитоплазми. Білок, що забезпечує автоімунітет до педіоцин-подібних бактеріоцинів, не секретується назовні, а є цитоплазма-тичним комплексом, пошкождує мембрану, зв'язуючись з ним з цитоплазма-тичного боку [52].…”

Bacteriocins from Lactic Acid Bacteria: A Review of Biosynthesis, Mode of Action, Fermentative Production, Uses, and Prospects

“…This group is oftentimes called pediocin-like because the first discovered bacteriocin belonging to this group was pediocin PA-1/AcH Drider et al 2006). While class IIb bacteriocins are twopeptide bacteriocins that require both peptides to work synergistically to be fully active (Oppegard et al 2007;Nissen-Meyer et al 2010), class IIc bacteriocins, arguably the most poorly understood, are grouped based on the circular configuration of their structure. The N-and C-termini of class IIc bacteriocins are covalently linked that results to a very stable molecular structure (Maqueda et al 2008;van Belkum et al 2011).…”