Conformation and ion channel properties of a five‐helix bundle protein

Abstract The primary amphipathic peptide Ac‐Met‐Gly‐Leu‐Gly‐Leu‐Trp‐Leu‐Leu‐Val‐Leu 10 ‐Ala‐Ala‐Ala‐Leu‐Gln‐Gly‐Ala‐Lys‐Lys‐Lys 20 ‐Arg‐Lys‐Val‐NH‐CH 2 ‐CH 2 ‐SH called SPM was able to induce formation of ion channels into planar lipid bilayers with main conductance values of 75 and 950 pS in 1 𝓂 KCl. The 75 pS value can be attributed to an aggregate composed of five monomers since the corresponding five‐unit bundle (5‐SPM) also presented a 70 pS channels under the same conditions. The upper 950 pS level would be generated by a hexameric aggregate. Ion channels induced by both SPM and its pentameric bundle are slightly cation selective but not voltage‐dependent. The structural studies showed that the SPM and 5‐SPM possess mainly an α‐helical structure (∼40%) and are strongly embedded in the bilayer. This behaviour and the strong hydrophobic interactions occurring between helices in the bundle induce a strong stabilization of 5‐SPM in the bilayer and would be responsible for the stepwise current fluctuations observed during the incorporation of 5‐SPM into the membrane. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.