The conformational analysis of a synthetic S4 peptide corresponding to a voltage-gated potassium ion channel protein.
The S4 region of the Drosophila Shaker voltage-gated K+ channel has been proposed to function as a voltage-sensor. We have synthesised a peptide corresponding to this S4 region. Structural studies on the S4 peptide were conducted using Fourier transform infrared (FTIR) spectroscopy. Spectra were obtained for the peptide dissolved in aqueous solution, in trifluoroethanol solvent and also after reconstitution into lipid bilayers and micelles. The peptide in trifluoroethanol adopts an alpha-helical conformation which is in good agreement with the results of a recent 2D NMR study on the structure of a S4 peptide corresponding to the rat brain sodium channel [(1989) FEBS Lett. 257, 113-117]. A predominantly alpha-helical structure is also observed when the S4 peptide is present in aqueous lysophosphatidylcholine micelles, in dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol lipid bilayers. In contrast to this, the S4 peptide in aqueous solution is in a random coil conformation. The coil-to-helix transition observed for the S4 peptide upon its transfer from aqueous solution to lipid membrane indicates that it has a high degree of conformational flexibility and can undergo large changes in its structure in response to its environment. This may have important implications for its role in the voltage activation process during which the S4 peptide has been postulated to, at least partially, move from a lipid bilayer to an aqueous extracellular media [(1992) Biophys J. 62, 238-250]. The results of our study lend support to such a model.
Haris
P I
PI
Department of Protein and Molecular Biology, Royal Free Hospital School of Medicine, University of London, UK.
Ramesh
B
B
Brazier
S
S
Chapman
D
D
D000595:Amino Acid Sequence; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D015221:Potassium Channels / Q000737:chemistry*; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
D010446:Peptide Fragments; D015221:Potassium Channels; C088750:S4 peptide, Drosophila Shaker potassium channel