title: The three-dimensional structure of carnocyclin A reveals that many circular bacteriocins share a common structural motif.
abstract: Carnocyclin A (CclA) is a potent antimicrobial peptide from Carnobacterium maltaromaticum UAL307 that displays a broad spectrum of activity against numerous Gram-positive organisms. An amide bond links the N and C termini of this bacteriocin, imparting stability and structural integrity to this 60-amino acid peptide. CclA interacts with lipid bilayers in a voltage-dependent manner and forms anion selective pores. Several other circular bacteriocins have been reported, yet only one (enterocin AS-48) has been structurally characterized. We have now determined the solution structure of CclA by NMR and further examined its anion binding and membrane channel properties. The results reveal that CclA preferentially binds halide anions and has a structure that is surprisingly similar to that of AS-48 despite low sequence identity, different oligomeric state, and disparate function. CclA folds into a compact globular bundle, comprised of four helices surrounding a hydrophobic core. NMR studies show two fluoride ion binding modes for CclA. Our findings suggest that although other circular bacteriocins are likely to have diverse mechanisms of action, many may have a common structural motif. This shared three-dimensional arrangement resembles the fold of mammalian saposins, peptides that either directly lyse membranes or serve as activators of lipid-degrading enzymes.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Martin-Visscher
authors.forename: Xiandi
authors.initials: X
authors.lastname: Gong
authors.forename: Marek
authors.initials: M
authors.lastname: Duszyk
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001430:Bacteriocins / Q000737:chemistry*; D007473:Ion Channels / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D049231:Saposins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D001430:Bacteriocins; D007473:Ion Channels; D008051:Lipid Bilayers; D010456:Peptides, Cyclic; D049231:Saposins; C531546:carnocyclin A, Carnobacterium maltaromaticum
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