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Proc Natl Acad Sci U S A. Jan 1990; 87(1): 210–214.
PMCID: PMC53231

Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes.

Abstract

Defensins are cationic, cysteine-rich peptides (Mr = 3500-4000) found in the cytoplasmic granules of neutrophils and macrophages. These peptides possess broad antimicrobial activity in vitro against bacteria, fungi, tumor cells, and enveloped viruses, and they are believed to contribute to the "oxygen-independent" antimicrobial defenses of neutrophils and macrophages. Pathophysiologic studies in vitro have pointed to the plasma membrane as a possible target for the cytotoxic action of defensins. We report here that defensins form voltage-dependent, weakly anion-selective channels in planar lipid bilayer membranes, and we suggest that this channel-forming ability contributes to their antimicrobial properties observed in vitro.

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  • Selsted ME, Brown DM, DeLange RJ, Lehrer RI. Primary structures of MCP-1 and MCP-2, natural peptide antibiotics of rabbit lung macrophages. J Biol Chem. 1983 Dec 10;258(23):14485–14489. [PubMed]
  • Selsted ME, Szklarek D, Lehrer RI. Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect Immun. 1984 Jul;45(1):150–154. [PMC free article] [PubMed]
  • Selsted ME, Brown DM, DeLange RJ, Harwig SS, Lehrer RI. Primary structures of six antimicrobial peptides of rabbit peritoneal neutrophils. J Biol Chem. 1985 Apr 25;260(8):4579–4584. [PubMed]
  • Selsted ME, Harwig SS. Purification, primary structure, and antimicrobial activities of a guinea pig neutrophil defensin. Infect Immun. 1987 Sep;55(9):2281–2286. [PMC free article] [PubMed]
  • Eisenhauer PB, Harwig SS, Szklarek D, Ganz T, Selsted ME, Lehrer RI. Purification and antimicrobial properties of three defensins from rat neutrophils. Infect Immun. 1989 Jul;57(7):2021–2027. [PMC free article] [PubMed]
  • Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. [PMC free article] [PubMed]
  • Selsted ME, Harwig SS, Ganz T, Schilling JW, Lehrer RI. Primary structures of three human neutrophil defensins. J Clin Invest. 1985 Oct;76(4):1436–1439. [PMC free article] [PubMed]
  • Lehrer RI, Ganz T, Selsted ME, Babior BM, Curnutte JT. Neutrophils and host defense. Ann Intern Med. 1988 Jul 15;109(2):127–142. [PubMed]
  • Lehrer RI, Barton A, Daher KA, Harwig SS, Ganz T, Selsted ME. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest. 1989 Aug;84(2):553–561. [PMC free article] [PubMed]
  • Patterson-Delafield J, Szklarek D, Martinez RJ, Lehrer RI. Microbicidal cationic proteins of rabbit alveolar macrophages: amino acid composition and functional attributes. Infect Immun. 1981 Feb;31(2):723–731. [PMC free article] [PubMed]
  • Lehrer RI, Daher K, Ganz T, Selsted ME. Direct inactivation of viruses by MCP-1 and MCP-2, natural peptide antibiotics from rabbit leukocytes. J Virol. 1985 May;54(2):467–472. [PMC free article] [PubMed]
  • Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986 Dec;60(3):1068–1074. [PMC free article] [PubMed]
  • Schein SJ, Kagan BL, Finkelstein A. Colicin K acts by forming voltage-dependent channels in phospholipid bilayer membranes. Nature. 1978 Nov 9;276(5684):159–163. [PubMed]
  • Montal M. Formation of bimolecular membranes from lipid monolayers. Methods Enzymol. 1974;32:545–554. [PubMed]
  • Lichtenstein A, Ganz T, Selsted ME, Lehrer RI. In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes. Blood. 1986 Dec;68(6):1407–1410. [PubMed]
  • Heyer RJ, Muller RU, Finkelstein A. Inactivation of monazomycin-induced voltage-dependent conductance in thin lipid membranes. II. Inactivation produced by monazomycin transport through the membrane. J Gen Physiol. 1976 Jun;67(6):731–748. [PMC free article] [PubMed]
  • Tosteson MT, Tosteson DC. The sting. Melittin forms channels in lipid bilayers. Biophys J. 1981 Oct;36(1):109–116. [PMC free article] [PubMed]
  • Sahl HG, Kordel M, Benz R. Voltage-dependent depolarization of bacterial membranes and artificial lipid bilayers by the peptide antibiotic nisin. Arch Microbiol. 1987;149(2):120–124. [PubMed]
  • Kordel M, Benz R, Sahl HG. Mode of action of the staphylococcinlike peptide Pep 5: voltage-dependent depolarization of bacterial and artificial membranes. J Bacteriol. 1988 Jan;170(1):84–88. [PMC free article] [PubMed]
  • Kagan BL. Mode of action of yeast killer toxins: channel formation in lipid bilayer membranes. Nature. 1983 Apr 21;302(5910):709–711. [PubMed]
  • Young JD, Peterson CG, Venge P, Cohn ZA. Mechanism of membrane damage mediated by human eosinophil cationic protein. Nature. 1986 Jun 5;321(6070):613–616. [PubMed]
  • Young JD, Cohn ZA, Podack ER. The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities. Science. 1986 Jul 11;233(4760):184–190. [PubMed]
  • Zasloff M. Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5449–5453. [PMC free article] [PubMed]
  • Christensen B, Fink J, Merrifield RB, Mauzerall D. Channel-forming properties of cecropins and related model compounds incorporated into planar lipid membranes. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5072–5076. [PMC free article] [PubMed]
  • Boman HG, Steiner H. Humoral immunity in Cecropia pupae. Curr Top Microbiol Immunol. 1981;94-95:75–91. [PubMed]
  • Muller RU, Finkelstein A. Voltage-dependent conductance induced in thin lipid membranes by monazomycin. J Gen Physiol. 1972 Sep;60(3):263–284. [PMC free article] [PubMed]
  • Oiki S, Danho W, Montal M. Channel protein engineering: synthetic 22-mer peptide from the primary structure of the voltage-sensitive sodium channel forms ionic channels in lipid bilayers. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2393–2397. [PMC free article] [PubMed]
  • Fox RO, Jr, Richards FM. A voltage-gated ion channel model inferred from the crystal structure of alamethicin at 1.5-A resolution. Nature. 1982 Nov 25;300(5890):325–330. [PubMed]
  • Wallace BA, Ravikumar K. The gramicidin pore: crystal structure of a cesium complex. Science. 1988 Jul 8;241(4862):182–187. [PubMed]
  • Langs DA. Three-dimensional structure at 0.86 A of the uncomplexed form of the transmembrane ion channel peptide gramicidin A. Science. 1988 Jul 8;241(4862):188–191. [PubMed]
  • Guy HR. A structural model of the acetylcholine receptor channel based on partition energy and helix packing calculations. Biophys J. 1984 Jan;45(1):249–261. [PMC free article] [PubMed]
  • Devillers-Thiery A, Giraudat J, Bentaboulet M, Changeux JP. Complete mRNA coding sequence of the acetylcholine binding alpha-subunit of Torpedo marmorata acetylcholine receptor: a model for the transmembrane organization of the polypeptide chain. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2067–2071. [PMC free article] [PubMed]
  • Claudio T, Ballivet M, Patrick J, Heinemann S. Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1111–1115. [PMC free article] [PubMed]
  • Noda M, Takahashi H, Tanabe T, Toyosato M, Furutani Y, Hirose T, Asai M, Inayama S, Miyata T, Numa S. Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature. 1982 Oct 28;299(5886):793–797. [PubMed]
  • Finer-Moore J, Stroud RM. Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor. Proc Natl Acad Sci U S A. 1984 Jan;81(1):155–159. [PMC free article] [PubMed]
  • Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, et al. Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family. Nature. 1987 Jul 16;328(6127):221–227. [PubMed]
  • Selsted ME, Harwig SS. Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide. J Biol Chem. 1989 Mar 5;264(7):4003–4007. [PubMed]
  • Paul C, Rosenbusch JP. Folding patterns of porin and bacteriorhodopsin. EMBO J. 1985 Jun;4(6):1593–1597. [PMC free article] [PubMed]
  • Bach AC, 2nd, Selsted ME, Pardi A. Two-dimensional NMR studies of the antimicrobial peptide NP-5. Biochemistry. 1987 Jul 14;26(14):4389–4397. [PubMed]
  • Pardi A, Hare DR, Selsted ME, Morrison RD, Bassolino DA, Bach AC., 2nd Solution structures of the rabbit neutrophil defensin NP-5. J Mol Biol. 1988 Jun 5;201(3):625–636. [PubMed]

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