TAILIEUCHUNG - Báo cáo khoa học: Distinguishing between different pathways of bilayer disruption by the related antimicrobial peptides cecropin B, B1 and B3

Different pathways of bilayer disruption by the structurally related antimicrobial peptides cecropin B, B1 and B3, revealed by surface plasma resonance analysis of immobi-lized liposomes, differential scanning calorimetryof peptide– large unilamellar vesicle interactions, and light microscopic analysis of peptide-treated giant unilamellar vesicles, have been identified inthis cecropinB(CB)hasone amphipathic and one hydrophobica-helix, whereas cecro-pins B1 (CB1) and B3 (CB3), which are custom-designed, chimaeric analogues of CB, possess either two amphipathic or two hydrophobica-helices, respectively | Eur. J. Biochem. 270 911-920 2003 FEBS 2003 doi Distinguishing between different pathways of bilayer disruption by the related antimicrobial peptides cecropin B B1 and B3 Hueih Min Chen1 King Wong Leung1 Nagendra N. Thakur1 Anmin Tan1 w and Ralph W. Jack2 Institute of BioAgricultural Sciences Academia Sinica Taipei Taiwan 2Institut fur Organische Chemie Universitat Tubingen Germany Different pathways of bilayer disruption by the structurally related antimicrobial peptides cecropin B B1 and B3 revealed by surface plasma resonance analysis of immobilized liposomes differential scanning calorimetry of peptide-large unilamellar vesicle interactions and light microscopic analysis of peptide-treated giant unilamellar vesicles have been identified in this study. Natural cecropin B CB has one amphipathic and one hydrophobic a-helix whereas cecro-pins B1 CB1 and B3 CB3 which are custom-designed chimaeric analogues of CB possess either two amphipathic or two hydrophobic a-helices respectively. Surface plasma resonance analysis of unilamellar vesicles immobilized through a biotin-avidin interaction showed that both CB and CB1 bind to the lipid bilayers at high concentration 10 M in contrast CB3 induces disintegration of the vesicles at all concentrations tested. Differential scanning calorimetry showed the concentration-dependent effect of bilayer disruption based on the different thermotrophic phase behaviours and the shapes of the thermal phasetransition curves obtained. The kinetics of the lysis of giant unilamellar vesicles observed by microscopy demonstrated that both CB and CB1 effect a continuous process involving loss of integrity followed by coalescence and resolution into smaller vesicles whereas CB3 induces rapid formation of irregular-shaped nonlamellar structures which rapidly disintegrate into twisted microtubule-containing debris before being completely destroyed. On the basis of these observations models by which CB CB1 and CB3

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