title: Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity.
abstract: Lacticin Q (LnqQ) and aureocin A53 (AucA) are leaderless bacteriocins from Lactococcus lactis QU5 and Staphylococcus aureus A53, respectively. These bacteriocins are characterized by the absence of an N-terminal leader sequence and are active against a broad range of Gram-positive bacteria. LnqQ and AucA consist of 53 and 51 amino acids, respectively, and have 47% identical sequences. In this study, their three-dimensional structures were elucidated using solution nuclear magnetic resonance and were shown to consist of four α-helices that assume a very similar compact, globular overall fold (root-mean-square deviation of 1.7 Å) with a highly cationic surface and a hydrophobic core. The structures of LnqQ and AucA resemble the shorter two-component leaderless bacteriocins, enterocins 7A and 7B, despite having low levels of sequence identity. Homology modeling revealed that the observed structural motif may be shared among leaderless bacteriocins with broad-spectrum activity against Gram-positive organisms. The elucidated structures of LnqQ and AucA also exhibit some resemblance to circular bacteriocins. Despite their similar overall fold, inhibition studies showed that LnqQ and AucA have different antimicrobial potency against the Gram-positive strains tested, suggesting that sequence disparities play a crucial role in their mechanisms of action.
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Jeella Z
authors.initials: JZ
authors.lastname: Acedo
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: van Belkum
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Lohans
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Kaitlyn M
authors.initials: KM
authors.lastname: Towle
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Mark
authors.initials: M
authors.lastname: Miskolzie
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, Canada T6G 2G2.
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D023181:Antimicrobial Cationic Peptides; D001430:Bacteriocins / Q000737:chemistry*; D013294:Lactococcus lactis / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: D023181:Antimicrobial Cationic Peptides; D001430:Bacteriocins; D010455:Peptides; C469333:aureocin A53, Staphylococcus aureus; C548356:lacticin Q, Lactococcus lactis