title: Peptaibol antiamoebin I: spatial structure, backbone dynamics, interaction with bicelles and lipid-protein nanodiscs, and pore formation in context of barrel-stave model.
abstract: Antiamoebin I (Aam-I) is a membrane-active peptaibol antibiotic isolated from fungal species belonging to the genera Cephalosporium, Emericellopsis, Gliocladium, and Stilbella. In comparison with other 16-amino acid-residue peptaibols, e.g., zervamicin IIB (Zrv-IIB), Aam-I possesses relatively weak biological and channel-forming activities. In MeOH solution, Aam-I demonstrates fast cooperative transitions between right-handed and left-handed helical conformation of the N-terminal (1-8) region. We studied Aam-I spatial structure and backbone dynamics in the membrane-mimicking environment (DMPC/DHPC bicelles)(1) ) by heteronuclear (1) H,(13) C,(15) N-NMR spectroscopy. Interaction with the bicelles stabilizes the Aam-I right-handed helical conformation retaining significant intramolecular mobility on the ms-μs time scale. Extensive ms-μs dynamics were also detected in the DPC and DHPC micelles and DOPG nanodiscs. In contrast, Zrv-IIB in the DPC micelles demonstrates appreciably lesser mobility on the μs-ms time scale. Titration with Mn(2+) and 16-doxylstearate paramagnetic probes revealed Aam-I binding to the bicelle surface with the N-terminus slightly immersed into hydrocarbon region. Fluctuations of the Aam-I helix between surface-bound and transmembrane (TM) state were observed in the nanodisc membranes formed from the short-chain (diC12 : 0) DLPC/DLPG lipids. All the obtained experimental data are in agreement with the barrel-stave model of TM pore formation, similarly to the mechanism proposed for Zrv-IIB and other peptaibols. The observed extensive intramolecular dynamics explains the relatively low activity of Aam-I.
authors.affiliation: Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia. zh@nmr.ru
authors.forename: Zakhar O
authors.initials: ZO
authors.lastname: Shenkarev
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Paramonov
authors.forename: Ekaterina N
authors.initials: EN
authors.lastname: Lyukmanova
authors.forename: Albina K
authors.initials: AK
authors.lastname: Gizatullina
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Zhuravleva
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Tagaev
authors.forename: Zoya A
authors.initials: ZA
authors.lastname: Yakimenko
authors.forename: Irina N
authors.initials: IN
authors.lastname: Telezhinskaya
authors.forename: Mikhail P
authors.initials: MP
authors.lastname: Kirpichnikov
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Ovchinnikova
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
mesh_terms: D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry; D054848:Peptaibols / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D016062:Porosity; D017433:Protein Structure, Secondary; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D008055:Lipids; D008823:Micelles; D054848:Peptaibols; D010455:Peptides; D014867:Water; C006596:antiamoebin