2L8X

Spatial structure of antimicrobial peptide Arenicin-2 dimer in DPC micelles

2L8X の概要

• エントリーDOI: 10.2210/pdb2l8x/pdb
• NMR情報: BMRB: 17430
• 分子名称: Arenicin-2 (1 entity in total)
• 機能のキーワード: arenicin, oligomerization, beta-hairpin, pore forming peptide, antimicrobial protein
• 由来する生物種: Arenicola marina (Lugworm)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 5560.75

構造登録者

Shenkarev, Z.O.,Trunov, K.I.,Paramonov, A.S.,Arseniev, A.S. (登録日: 2011-01-27, 公開日: 2011-12-14, 最終更新日: 2024-10-09)

主引用文献

Shenkarev, Z.O.,Balandin, S.V.,Trunov, K.I.,Paramonov, A.S.,Sukhanov, S.V.,Barsukov, L.I.,Arseniev, A.S.,Ovchinnikova, T.V.
Molecular mechanism of action of beta-hairpin antimicrobial peptide arenicin: oligomeric structure in dodecylphosphocholine micelles and pore formation in planar lipid bilayers
Biochemistry, 50:6255-6265, 2011

PubMed Abstract: The membrane-active, cationic, β-hairpin peptide, arenicin, isolated from marine polychaeta Arenicola marina exhibits a broad spectrum of antimicrobial activity. The peptide in aqueous solution adopts the significantly twisted β-hairpin conformation without pronounced amphipathicity. To assess the mechanism of arenicin action, the spatial structure and backbone dynamics of the peptide in membrane-mimicking media and its pore-forming activity in planar lipid bilayers were studied. The spatial structure of the asymmetric arenicin dimer stabilized by parallel association of N-terminal strands of two β-hairpins was determined using triple-resonance nuclear magnetic resonance (NMR) spectroscopy in dodecylphosphocholine (DPC) micelles. Interaction of arenicin with micelles and its oligomerization significantly decreased the right-handed twist of the β-hairpin, increased its amphipathicity, and led to stabilization of the peptide backbone on a picosecond to nanosecond time scale. Relaxation enhancement induced by water-soluble (Mn(2+)) and lipid-soluble (16-doxylstearate) paramagnetic probes pointed to the dimer transmembrane arrangement. Qualitative NMR and circular dichroism study of arenicin-2 in mixed DPC/1,2-dioleoyl-sn-glycero-3-phosphoglycerol bicelles, sodium dodecyl sulfate micelles, and lipid vesicles confirmed that a similar dimeric assembly of the peptide was retained in membrane-mimicking systems containing negatively charged lipids and detergents. Arenicin-induced conductance was dependent on the lipid composition of the membrane. Arenicin low-conductivity pores were detected in the phosphatidylethanolamine-containing lipid mixture, whereas the high-conductivity pores were observed in an exclusively anionic lipid system. The measured conductivity levels agreed with the model in which arenicin antimicrobial activity was mediated by the formation of toroidal pores assembled of two, three, or four β-structural peptide dimers and lipid molecules. The structural transitions involved in arenicin membrane-disruptive action are discussed.

PubMed: 21627330
DOI: 10.1021/bi200746t

実験手法

SOLUTION NMR