A synthetic S6 segment derived from KvAP channel self-assembles, permeabilizes lipid vesicles, and exhibits ion channel activity in bilayer lipid membrane

J Biol Chem. 2011 Jul 15;286(28):24828-41. doi: 10.1074/jbc.M110.209676. Epub 2011 May 18.


KvAP is a voltage-gated tetrameric K(+) channel with six transmembrane (S1-S6) segments in each monomer from the archaeon Aeropyrum pernix. The objective of the present investigation was to understand the plausible role of the S6 segment, which has been proposed to form the inner lining of the pore, in the membrane assembly and functional properties of KvAP channel. For this purpose, a 22-residue peptide, corresponding to the S6 transmembrane segment of KvAP (amino acids 218-239), and a scrambled peptide (S6-SCR) with rearrangement of only hydrophobic amino acids but without changing its composition were synthesized and characterized structurally and functionally. Although both peptides bound to the negatively charged phosphatidylcholine/phosphatidylglycerol model membrane with comparable affinity, significant differences were observed between these peptides in their localization, self-assembly, and aggregation properties onto this membrane. S6-SCR also exhibited reduced helical structures in SDS micelles and phosphatidylcholine/phosphatidylglycerol lipid vesicles as compared with the S6 peptide. Furthermore, the S6 peptide showed significant membrane-permeabilizing capability as evidenced by the release of calcein from the calcein-entrapped lipid vesicles, whereas S6-SCR showed much weaker efficacy. Interestingly, although the S6 peptide showed ion channel activity in the bilayer lipid membrane, despite having the same amino acid composition, S6-SCR was significantly inactive. The results demonstrated sequence-specific structural and functional properties of the S6 wild type peptide. The selected S6 segment is probably an important structural element that could play an important role in the membrane interaction, membrane assembly, and functional property of the KvAP channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aeropyrum / chemistry*
  • Aeropyrum / genetics
  • Aeropyrum / metabolism
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism
  • Cell Membrane Permeability*
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Structure-Activity Relationship


  • Archaeal Proteins
  • Lipid Bilayers
  • Peptides
  • Potassium Channels