Magainin Oligomers Reversibly Dissipate .DELTA..mu.H+ in Cytochrome Oxidase Liposomes

Abstract

Magainin oligomers reversibly dissipate DeltamuH in cytochrome oxidase liposomes.Juretic, D.; Hendler, R.W.; Kamp, F.; Caughey, W.S.; Zasloff, M.; Westerhoff, H.V. Published in: Biochemistry DOI:10.1021/bi00181a017Link to publication Citation for published version (APA):Juretic, D., Hendler, R. W., Kamp, F., Caughey, W. S., Zasloff, M., & Westerhoff, H. V. (1994). Magainin oligomers reversibly dissipate DeltamuH in cytochrome oxidase liposomes. Biochemistry, 33, 4562-4570. DOI: 10.1021/bi00181a017 General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. as a monomer to the membranes but equilibrates with a multimeric pore that causes rather general permeability of membranes. The ensuing ion permeation dissipates membrane potential and stimulates respiration.The skin of amphibia and reptiles has been a rich source of biologically active compounds (Witkop & Goessinger, 1983). This was again stressed by the observation that the skin of Xenopus laevis actively secretes numerous peptides (Gibson et al., 1986;Giovannini et al., 1987) and the demonstration (Zasloff, 1987;Soravia et al., 1988;De Waal et al., 1991;Baker et al., 1993) that at least three of these, Le., magainin 1, magainin 2,' and PGLa, to which we shall collectively refer as magainins, are cytotoxic for microbial and higher eukaryotic cells. Synthetic analogues of these magainins have been shown to be even more active in antimicrobial assays than the parent compounds JuretiC et al., 1989). Magainins may be part of a structurally heterogeneous, but functionally definable, class of oligopeptides (Boman & Hultmark, 1987;Dimarcq et al., 1988;Lehrer et al, 1988;Nakajima et al., 1987; Bevins & Zasloff, 1990; Boman, 199 1) that provide a secondary immune system for organisms as diverse as insects, amphibia, and man.At pH 7, magainins are positively charged, amphiphilic oligopeptides consisting of some 23 amino acids (Zasloff, 1987; f This study was supported by the Netherlands Organization for Scientific Research (NWO).

Mode of action of linear amphipathic α-helical antimicrobial peptides

“…The positive cooperativity of membrane permeabilization by magainin as observed in different systems occurred at relatively high peptide/lipid molar ratios after a threshold concentration had been reached. This implied that the association of lipid-bound magainin is important for its activity, 89,113,120,121 whereas no direct evidence was found of magainin association in its membrane-bound state at low peptide : lipid molar ratio. A fluorescence energy transfer study 122 revealed that the experimentally determined transfer efficiency is lower than predicted for monomeric magainin analogues that randomly distributed exclusively at the outer leaflet of lipid vesicles.…”

“…84,[87][88][89]120,126,130,131 A few examples demonstrate this effect: (a) The kinetics of magainin-2 induced release of 6-carboxyfluorescein (CF) from phosphatidylserine liposomes indicating that the fast release of dye is a transient effect resulting from transient destabilization of the bilayer upon initial interaction with the peptide. 131 No measurable CF release could be observed until a high level of bound magainin was achieved; (b) The ability of magainin-2 to decrease the membrane potential in cytochrome oxidase liposomes was investigated by Juretic et al 120 At low concentrations the peptide was almost inactive, but activity was observed when a critical concentration was reached. (c) Neutron in-plane scattering detects pores formed by magainin-2 in membranes only when a substantial fraction of the peptide is oriented perpendicular to the membrane.…”

The Interactions of Histidine-containing Amphipathic Helical Peptide Antibiotics with Lipid Bilayers

“…Experimental evidence suggests that direct peptide-lipid interactions are important for the expression of antibiotic activity of these substances (18), rather than specific association with a chiral receptor. In particular, the first recognition and membrane association is strongly governed by electrostatic interactions with the negative surface charges of the bacterial cell wall and/or the plasma membrane (19,20).There is good agreement that this class of polypeptides exerts its antibiotic activity by permeabilizing the membranes of sensitive cells, which results in decoupling of the transmembrane ionic gradients and consecutively cell death (21,22). The mechanisms of membrane permeabilization are, however, unknown and several models have been proposed to explain the interaction of polypeptides with lipid bilayers (23).…”

“…Magainins and related peptides have been shown to decouple the ionic gradients across the cell membranes of sensitive organisms (22), cytochrome oxidase liposomes (21), as well as model membranes (34). Similarly, 1-anilinonaphtalene-8-sulfonic acid fluorescence spectroscopy indicates that LAH 4 destroys the transmembrane electric potential of living E. coli cells.…”

Towards Membrane Protein Design: pH-sensitive Topology of Histidine-containing Polypeptides

“…Immunogenic peptides, including cecropins or magainins for example, provide an immediate response system, fighting both infections (Bevins & Zasloff, 1990;Boman, 1991) and cancer development (Ohsaki et al, 1992;Baker et al, 1993). It has been suggested that these peptides form transmembrane oligomeric channels (Cruciani et al, 1992;Duclohier, 1994;Juretic et al, 1994), although structural investigations indicate that they assume an orientation parallel with the bilayer surface (Bechinger et al, , 1993Matzusaki et al, 1994). The possibility remains, however, that the measured electrophysiological activity is caused by a minor fraction of peptide in a transmembrane orientation, too small to be detected during structural investigations.…”