title: Molecular insight into mechanism of antimicrobial action of the beta-hairpin peptide arenicin: specific oligomerization in detergent micelles.
abstract: Arenicins are 21-residue cationic antimicrobial peptides isolated from marine polychaeta Arenicola marina. The peptides exhibit potent broad-spectrum antimicrobial activity. In water solution arenicin-2 adopts a beta-hairpin conformation, stabilized by one disulfide and nine hydrogen bonds. To determine the propensity for the peptide oligomerization in membrane mimetic systems, the recombinant arenicin-2 was overexpressed as a fused form in Escherichia coli. The arenicin-2 oligomerization and intermolecular packing in membrane mimicking environment were investigated using high-resolution NMR spectroscopy. The present studies show that arenicin-2 preserves a beta-hairpin structure and forms asymmetric dimers upon incorporation into the dodecylphosphocholine micelle. Two monomers of arenicin-2 are aligned parallel to each other by the N-terminal strands of the beta-hairpin (CN upward arrow upward arrowNC type of association). Polyacrylamide gel electrophoresis analysis indicated that in environment of anionic SDS micelles the arenicin-2 might undergo further oligomerization and form tetramers. Our results afford further molecular insight into possible mechanism of antimicrobial action of arenicins.
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia. ovch@ibch.ru
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Ovchinnikova
authors.forename: Zakhar O
authors.initials: ZO
authors.lastname: Shenkarev
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Balandin
authors.forename: Kirill D
authors.initials: KD
authors.lastname: Nadezhdin
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Paramonov
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Kokryakov
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000302:isolation & purification; D003902:Detergents / Q000737:chemistry* / Q000494:pharmacology; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D015801:Helminth Proteins; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D023181:Antimicrobial Cationic Peptides; D003902:Detergents; D015801:Helminth Proteins; D008823:Micelles; D010455:Peptides; C496888:arenicin-1, Arenicola marina; D010767:Phosphorylcholine; C028810:dodecylphosphocholine