2M1F

NMR Structure of Antiamoebin I (peptaibol antibiotic) bound to DMPC/DHPC bicelles

Summary for 2M1F

• Entry DOI: 10.2210/pdb2m1f/pdb
• Related: 1DLZ 1IH9 1JOH 1OB4 1OB6 1OB7 1R9U
• NMR Information: BMRB: 18861
• Related PRD ID: PRD_000161
• Descriptor: Antiamoebin I (1 entity in total)
• Functional Keywords: membrane-active, peptaibol, antibiotic
• Biological source: Emericellopsis minima
• Total number of polymer chains: 1
• Total formula weight: 1654.99

Authors

Shenkarev, Z.O.,Paramonov, A.S.,Gizatullina, A.K. (deposition date: 2012-11-27, release date: 2012-12-12, Last modification date: 2025-03-26)

Primary citation

Shenkarev, Z.O.,Paramonov, A.S.,Lyukmanova, E.N.,Gizatullina, A.K.,Zhuravleva, A.V.,Tagaev, A.A.,Yakimenko, Z.A.,Telezhinskaya, I.N.,Kirpichnikov, M.P.,Ovchinnikova, T.V.,Arseniev, A.S.
Peptaibol antiamoebin I: spatial structure, backbone dynamics, interaction with bicelles and lipid-protein nanodiscs, and pore formation in context of barrel-stave model.
Chem.Biodivers., 10:838-863, 2013

PubMed 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.

PubMed: 23681729
DOI: 10.1002/cbdv.201200421

Experimental method

SOLUTION NMR