1. Influence of proline-14 substitution on the secondary structure in a synthetic analogue of alamethicin.
- Author
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Brachais L, Duclohier H, Mayer C, Davoust D, and Molle G
- Subjects
- Amino Acid Sequence, Circular Dichroism, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Peptides chemical synthesis, Structure-Activity Relationship, Alamethicin chemistry, Peptides chemistry, Proline, Protein Structure, Secondary
- Abstract
Due to the bend introduced by proline 14 in the conformation of alamethicin (AcUPUAUAQUVUGLUPV UUEQFol), the role of this residue was assumed essential in the barrel-stave model for voltage-gated ion channels. Taking advantage of a previous synthetic alamethicin analogue (L2), in which all eight alpha-aminoisobutyric (U) were replaced by leucines (AcLPLALAQLV LGLLPV LLEQFol), another analogue (L5) was synthesized in order to test the effects of proline-14 substitution by an alanine (AcLPLALAQLVLGLLPVLLEQFol). Previous conductance experiments showed that both high voltage dependence and multistate behavior were conserved. In order to complement these functional results, a conformational study of L5 has been undertaken and compared to L2 using CD, high field nmr, and molecular dynamics. Results show that L5 presents a better ordered structure than L2 particularly in the region of the substitution and in the C-terminal part. These results are discussed as regards the previous hypothesis of the nonessential character of helix bending for the gating of voltage-dependent ion channels.
- Published
- 1995
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