Heterodimer formation between the antimicrobial peptides magainin 2 and PGLa in lipid bilayers: a cross-linking study.
The antimicrobial peptides magainin 2 and PGLa, isolated from the skin of the African clawed frog Xenopus laevis, show marked synergism [Westerhoff, H. V., Zasloff, M., Rosner, J. L., Hendler, R. W., de Waal, A., Vaz Gomes, A., Jongsma, A. P. M., Riethorst, A., and Juretic, D. (1995) Eur. J. Biochem. 228, 257-264]. We suggested previously that these peptides form a potent heterodimer composed of either parallel or antiparallel helices in membranes [Matsuzaki, K., Mitani, Y., Akada, K., Murase, O., Yoneyama, S., Zasloff, M., and Miyajima, K. (1998) Biochemistry 37, 15144-15153]. To detect the putative heterodimer by chemical cross-linking, analogues of magainin 2 and PGLa with a Cys residue at either terminus were synthesized. These cross-linking experiments suggested that both peptides form a parallel heterodimer in membranes composed of phosphatidylglycerol/phosphatidylcholine but not in either buffer or a helix-promoting 2,2,2-trifluoroethanol/buffer mixture. The isolated parallel heterodimers exhibited an order of magnitude higher membrane permeabilization activity compared with the monomeric species, indicating that the observed synergism is due to heterodimer formation.
Hara
T
T
Department of Chemistry, Faculty of Science and Engineering, Saga University, Saga 840-8502, Japan.
Mitani
Y
Y
Tanaka
K
K
Uematsu
N
N
Takakura
A
A
Tachi
T
T
Kodama
H
H
Kondo
M
M
Mori
H
H
Otaka
A
A
Nobutaka
F
F
Matsuzaki
K
K
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D003432:Cross-Linking Reagents; D019281:Dimerization; D015195:Drug Design; D004357:Drug Synergism; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D054806:Magainins; D008969:Molecular Sequence Data; D010539:Permeability; D011498:Protein Precursors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D029867:Xenopus Proteins; D014982:Xenopus laevis
D023181:Antimicrobial Cationic Peptides; D003432:Cross-Linking Reagents; D008051:Lipid Bilayers; D054806:Magainins; C088254:PGLa prepropeptide; D011498:Protein Precursors; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus