Environment- and Sequence-Dependent Modulation of the Double-Stranded to Single-Stranded Conformational Transition of Gramicidin A in Membranes

• DOI: 10.1021/bi980733k
• Publication Date: 2002-07-26T05:19:13Z
• Authors: David Salom; Enrique Pérez-Payá; Jeanick Pascal; Concepción Abad
• Keywords: Gramicidin S; Residue (chemistry); Conformational change

The role of the membrane lipid composition and individual Trp residues in conformational rearrangement gramicidin A along folding pathway to its channel conformation has been examined phospholipid bilayers by means previously described size-exclusion high-performance liquid chromatography HPLC-based strategy (Bañó et al. (1991) Biochemistry 30, 886). It demonstrated that chemical influences transition rate peptide from double-stranded dimers β-helical monomers. modification residues, or substitution more hydrophobic phenylalanine naphthylalanine, stabilized dimer model membranes. This effect was notable as number Trp-substituted increased (tetra > tri di mono), it also influenced specific position substituted amino acid residue sequence, order Trp-9 ≈ Trp-13 Trp-11 Trp-15. Moreover, verified nearly a full contingent indoles (Trp-13, -11, -9) is necessary induce quantitative conversion single-stranded monomers, although seemed be key for stabilization monomeric A. adopted → Phe analogues vesicles resulted CD spectra similar typical β6.3-helical However, showed decreased antibiotic activity decreased.