Interaction of hagfish cathelicidin antimicrobial peptides with model lipid membranes

FEBS Letters

Shinnar, Ann E¹  Basañez, Gorka³  Zimmerberg, Joshua² 

[1] Chemistry Department, Barnard College, New York, NY 10027, USA;Laboratory of Cellular and Molecular Biophysics, National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA;Unidad de Biofı́sica (Centro Mixto UPV/CSIC), y Departamento de Bioquı́mica y Biologı́a Molecular, Universidad del Pais Vasco (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain

关键词: Antimicrobial peptides;    Innate immunity;    Cathelicidin;    Hagfish;    Lipidic pore;    Membrane curvature;    ANTS;    8-aminonaphtalene-1;    3;    6-trisulfonate;    CHOL;    cholesterol;    DG;    dioleoylglycerol;    DPX;    p-xylene-bis-pyridinium bromide;    FD-4;    fluorescein isothiocyanate-labeled dextrans of ∼4 kDa;    FD-70;    fluorescein isothiocyanate-labeled dextrans of ∼70 kDa;    HFIAP;    hagfish intestinal antimicrobial peptide;    LPC;    oleoylphosphatidycholine;    LPE;    oleoylphosphatidylethanolamine;    LUV;    large unilamellar vesicles;    OA;    oleic acid;    PC;    dioleoylphosphatidylcholine;    PE;    dioleoylphosphatidylethanolamine;    PG;    dioleoylphosphatidylglycerol;    Pyr-PC;    1-lauroyl-2-(1′ pyrenebutyroyl)-sn-glycero-3-phosphocholine;    SM;    sphingomyelin;   

DOI  :  10.1016/S0014-5793(02)03651-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Hagfish intestinal antimicrobial peptides (HFIAPs) are a family of polycationic peptides exhibiting potent, broad-spectrum bactericidal activity. In an attempt to unravel the mechanism of action of HFIAPs, we have studied their interaction with model membranes. Synthetic HFIAPs selectively bound to liposomes mimicking bacterial membranes, and caused the release of vesicle-encapsulated fluorescent markers in a size-dependent manner. In planar lipid bilayer membranes, HFIAPs induced erratic current fluctuations and reduced membrane line tension according to a general theory for lipidic pores, suggesting that HFIAP pores contain lipid molecules. Consistent with this notion, lipid transbilayer redistribution accompanied HFIAP pore formation, and membrane monolayer curvature regulated HFIAP pore formation. Based on these studies, we propose that HFIAPs kill target cells, at least in part, by interacting with their plasma membrane to induce formation of lipid-containing pores. Such a membrane-permeabilizing function appears to be an evolutionarily conserved host-defense mechanism of antimicrobial peptides.

【 授权许可】

Unknown