Tachyplesin I (T-SS), an antimicrobial peptide from Tachypleus tridentatus, has a cyclic antiparallel β-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., and 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.
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