Peptaibol Antiamoebin I: Spatial Structure, Backbone Dynamics, Interaction with Bicelles and Lipid‐Protein Nanodiscs, and Pore Formation in Context of Barrel‐Stave Model. Issue 5 (17th May 2013)

• Record Type: Journal Article
• Authors: Shenkarev, Zakhar O.; Paramonov, Alexander S.; Lyukmanova, Ekaterina N.; Gizatullina, Albina K.; Zhuravleva, Anastasia V.; Tagaev, Andrey A.; Yakimenko, Zoya A.; Telezhinskaya, Irina N.; Kirpichnikov, Mikhail P.; Ovchinnikova, Tatiana V.; Arseniev, Alexander S.
• Is Part Of: Chemistry & biodiversity. Volume 10:Issue 5(2013:May)
• Page Start: 838
• Page End: 863
• Publication Date: 2013-05-17
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.201200421
• Languages: English
• ISSNs: 1612-1872

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Antiamoebin I (Aam‐I) is a membrane‐active peptaibol antibiotic isolated from fungal species belonging to the genera <italic>Cephalosporium, Emericellopsis, Gliocladium</italic>, and <italic>Stilbella.</italic> In comparison with other 16‐amino acid‐residue peptaibols, <italic>e.g.</italic>, 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)<sup>1</sup>) by heteronuclear <sup>1</sup>H, <sup>13</sup>C, <sup>15</sup>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<sup>2+</sup> 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.</p> </abstract>