title: Mutational analysis of the class IIa bacteriocin curvacin A and its orientation in target cell membranes.
abstract: To analyze the orientation in target cell membranes of the pediocin-like bacteriocin (antimicrobial peptide) curvacin A, 55 variants were generated by site-directed mutagenesis and their potencies against four different target cells determined. The result suggest that the somewhat hydrophilic short central helix (residues 19 to 24), along with the N-terminal beta-sheet-like structure (residues 1 to 16), inserts in the interface region of the target cell membrane, with Ala22 close to the hydrophobic core of the membrane. The following hinge region, with Gly28 as an important residue, may then form a turn wherein Gly28 becomes positioned near the border between the interface and the hydrophobic regions, thus permitting the longer and more-hydrophobic C-terminal helix (residues 29 to 41) to insert into the hydrophobic core of the membrane. This helix contains three glycine residues (G33, G37, and G40) that form a putative helix-helix-interacting GxxxGxxG motif. The replacement of any of these glycines with a larger residue was very detrimental, suggesting their possible involvement in helix-helix interactions with a membrane-embedded receptor protein.
authors.affiliation: Department of Molecular Biosciences, University of Oslo, Oslo, Norway. h.s.haugen@imbv.uio.no
authors.forename: Helén Sophie
authors.initials: HS
authors.lastname: Haugen
authors.forename: Per Eugen
authors.initials: PE
authors.lastname: Kristiansen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Fimland
authors.forename: Jon
authors.initials: J
authors.lastname: Nissen-Meyer
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001430:Bacteriocins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry*; D004252:DNA Mutational Analysis; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C071456:sakacin A
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