title: Influence of proline-14 substitution on the secondary structure in a synthetic analogue of alamethicin.
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.
authors.affiliation: URA 500 CNRS (Inst. Fed. Rech. Mult. Peptides) Université de Rouen, Mont-Saint-Aignan, France.
authors.forename: L
authors.initials: L
authors.lastname: Brachais
authors.forename: H
authors.initials: H
authors.lastname: Duclohier
authors.forename: C
authors.initials: C
authors.lastname: Mayer
authors.forename: D
authors.initials: D
authors.lastname: Davoust
authors.forename: G
authors.initials: G
authors.lastname: Molle
mesh_terms: D000408:Alamethicin / Q000737:chemistry*; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011392:Proline; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D000408:Alamethicin; D011392:Proline