Characterization of a type of β-bend ribbon spiral generated by the repeating (Xaa–Yaa–Aib–Pro) motif: The solution structure of harzianin HC IX, a 14-residue peptaibol forming voltage-dependent ion channels
✍ Scribed by Isabelle Ségalas; Yann Prigent; Daniel Davoust; Bernard Bodo; Sylvie Rebuffat
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1999
- Tongue
- English
- Weight
- 267 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
The three-dimensional solution structure of harzianin HC IX, a peptaibol antibiotic isolated from the fungus Trichoderma harzianum, was determined using CD, homonuclear, and heteronuclear two-dimensional nmr spectroscopy combined with molecular modeling. This 14residue peptide, Ac Aib 1 Asn 2 Leu 3 Aib 4 Pro 5 Ala 6 Ile 7 Aib 8 Pro 9 Iva 10 Leu 11 Aib 12 Pro 13 Leuol 14 (Aib, ␣-aminoisobutyric acid; Iva, isovaline; Leuol, leucinol), is a main representative of a short-sequence peptaibol class characterized by an acetylated N-terminus, a C-terminal amino alcohol, and the presence of three Aib-L-Pro motifs at positions 4 -5, 8 -9, and 12-13, separated by two dipeptide units. In spite of a lower number of residues, compared to the 18/20-residue peptaibols such as alamethicin, harzianin HC IX exhibits remarkable membrane-perturbing properties. It interacts with phospholipid bilayers, increasing their permeability and forming voltagegated ion channels through a mechanism slightly differing from that proposed for alamethicin. Sequence-specific 1 H-and 13 C-nmr assignments and conformational nmr parameters ( 3 J NHC␣H coupling constants, quantitative nuclear Overhauser enhancement data, temperature coefficients of amide and carbonyl groups, NH-ND exchange rates) were obtained in methanol solution. Sixty structures were calculated based on 98 interproton distance restraints and 6 ⌽ dihedral angle restraints, using high temperature restrained molecular dynamics and energy minimization. Thirtyseven out of the sixty generated structures were consistent with the nmr data and were convergent. The peptide backbone consists in a ribbon of overlapping -turns twisted into a continuous spiral