title: Mirror Images of Antimicrobial Peptides Provide Reflections on Their Functions and Amyloidogenic Properties.
abstract: Enantiomeric forms of BTD-2, PG-1, and PM-1 were synthesized to delineate the structure and function of these β-sheet antimicrobial peptides. Activity and lipid-binding assays confirm that these peptides act via a receptor-independent mechanism involving membrane interaction. The racemic crystal structure of BTD-2 solved at 1.45 Å revealed a novel oligomeric form of β-sheet antimicrobial peptides within the unit cell: an antiparallel trimer, which we suggest might be related to its membrane-active form. The BTD-2 oligomer extends into a larger supramolecular state that spans the crystal lattice, featuring a steric-zipper motif that is common in structures of amyloid-forming peptides. The supramolecular structure of BTD-2 thus represents a new mode of fibril-like assembly not previously observed for antimicrobial peptides, providing structural evidence linking antimicrobial and amyloid peptides.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Conan K
authors.initials: CK
authors.lastname: Wang
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: King
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Conibear
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Ramos
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chaousis
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Sónia Troeira
authors.initials: ST
authors.lastname: Henriques
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D020349:Surface Plasmon Resonance
chemical_list: D000682:Amyloid; D000890:Anti-Infective Agents; D010455:Peptides