期刊
CHEMISTRY & BIODIVERSITY
卷 10, 期 5, 页码 838-863出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbdv.201200421
关键词
Antiamoebin I; Peptaibols; Membrane-mimicking environment; Intramolecular dynamics; Barrel-stave model
资金
- Russian Foundation for Basic Research [10-04-01752, 12-04-1224]
- Russian Federal Target Program 'Scientific and Science-Educational Personnel of Innovative Russia' [8789, 8043]
- Russian Academy of Sciences (Program 'Molecular and Cellular Biology')
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 (18) region. We studied Aam-I spatial structure and backbone dynamics in the membrane-mimicking environment (DMPC/DHPC bicelles)1) by heteronuclear 1H,13C,15N-NMR spectroscopy. Interaction with the bicelles stabilizes the Aam-I right-handed helical conformation retaining significant intramolecular mobility on the mss time scale. Extensive mss 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 sms time scale. Titration with Mn2+ 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.
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