MEMBRANE PERMEABILIZATION MECHANISMS OF A CYCLIC ANTIMICROBIAL PEPTIDE, TACHYPLESIN-I, AND ITS LINEAR ANALOG

Tachyplesin I (T-SS), an antimicrobial peptide from Tachypleus trident atus, has a cyclic antiparallel beta-sheet structure maintained by two disulfide bridges. The peptide effectively permeabilizes both bacteri al and artificial lipid membranes. T-Acm, a linear analog peptide with the four SH groups protected by acetamidomethyl groups, exhibits a mu ch weaker membrane-permeabilizing activity in spite of a greater disru ption of the lipid organization [Matsuzaki, K., Nakayama, M., Fukui, M ., Otaka, A., Funakoshi, S., Fujii, N., Bessho, K., & Miyajima, K. (19 93) Biochemistry 32, 11704-11710]. To clarify the efficient permeabili zation 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-s elective pore and translocate across the bilayer coupled with the pore formation. A cis-negative transmembrane potential facilitated the por e formation compared with the cis-positive potential. In contrast, the linear peptide failed to translocate. Instead, it impaired the membra ne barrier by disrupting the lipid organization with morphological cha nges in the vesicles.