Membrane permeabilization mechanisms of a cyclic antimicrobial peptide, tachyplesin I, and its linear analog.
Tachyplesin I (T-SS), an antimicrobial peptide from Tachypleus tridentatus, has a cyclic antiparallel beta-sheet structure maintained by two disulfide bridges. The peptide effectively permeabilizes both bacterial and artificial lipid membranes. T-Acm, a linear analog peptide with the four SH groups protected by acetamidomethyl groups, exhibits a much weaker membrane-permeabilizing activity in spite of a greater disruption of the lipid organization [Matsuzaki, K., Nakayama, M., Fukui, M., Otaka, A., Funakoshi, S., Fujii, N., Bessho, K., & Miyajima, K. (1993) Biochemistry 32, 11704-11710]. To clarify the efficient permeabilization mechanism of T-SS, we studied the interactions of both peptides with liposomes and planar lipid bilayers. The cyclic peptide capable of spanning the bilayer (ca. 3 nm length) was found to form an anion-selective pore and translocate across the bilayer coupled with the pore formation. A cis-negative transmembrane potential facilitated the pore formation compared with the cis-positive potential. In contrast, the linear peptide failed to translocate. Instead, it impaired the membrane barrier by disrupting the lipid organization with morphological changes in the vesicles.
Matsuzaki
K
K
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Yoneyama
S
S
Fujii
N
N
Miyajima
K
K
Yamada
K
K
Kirino
Y
Y
Anzai
K
K
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001692:Biological Transport / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000378:metabolism* / Q000494:pharmacology; D010539:Permeability; D010713:Phosphatidylcholines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D010456:Peptides, Cyclic; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C057636:tachyplesin peptide, Tachypleus tridentatus