Three-dimensional structure of the ion-chanel forming peptide trichorzianin TA VII bound to sodium dodecyl sulfate micelles

Trichorzianin TA VII, Ac⁰ U¹ A² A³ U⁴ J⁵ Q⁶ U⁷ U⁸ U⁹ S¹⁰ L¹¹ U¹² P¹³ V¹⁴ U¹⁵ I¹⁶ Q¹⁷ Q¹⁸ Fol¹⁹, is a nonadecapeptide member of the peptaibol antibiotics biosynthesized by Trichoderma soil fungi, which is characterized by a high proportion of the α,α-dialkylated amino acids, α-aminoisobutyric acid (Aib, U) and isovaline (Iva, J), an acetylated N-terminus and a C-terminal phenylalaninol (Pheol, Fol). The main interest in such peptides stems from their ability to interact with phospholipid bilayers and form voltage-dependent transmembrane channels in planar lipid bilayers. In order to provide insights into the lipid-peptide interaction promoting the voltage gating, the conformational study of TA VII in the presence of perdeuterated sodium dodecyl sulfate (SDS-d25) micelles has been carried out. ¹H sequential assignments have been performed with the use of two-dimensional homo- and -heteronuclear nmr techniques including double quantum filtered correlated spectroscopy, homonuclear Hartmann-Hahn, nuclear Overhauser effect spectroscopy, ¹H-¹³C heteronuclear single quantum correlation, and heteronuclear multiple bond correlation. Conformational parameters, such as ³ J _NHCαH coupling constants, temperature coefficients of amide protons (Δδ/Δ T _NH) and quantitative nuclear Overhauser enhancement data, lead to detailed structural information. Ninety-eight three-dimensional structures consistent with the nmr data were generated from 231 interproton distances and six Φ dihedral angle restraints, using restrained molecular dynamics and energy minimization calculations. The average rms deviation between the 98 refined structures and the energy-minimized average structure is 0.59 Å for the backbone atoms. The structure of trichorzianin TA VII associated with SDS micelles, as determined by these methods, is characterized by two right-handed helical segments involving residues 1–8 and 11–19, linked by a β-turn that leads to an angle about 90°–100° between the two helix axes; residues 18 and 19 at the end of the C-terminal helix exhibit multiple conformations. © 1998 John Wiley & Sons, Inc. Biopoly 46: 75–88, 1998