Aiming to identify structural motifs involved in its effects, mutated versions of jaburetox were built: 1) a peptide lacking the 尾-hairpin motif (residues 61-74), Jbtx螖-尾; 2) a peptide corresponding the N-terminal half (residues 1-44), Jbtx N-ter, and 3) a peptide corresponding the C-terminal half (residues 45-93), Jbtx C-ter.
1) Jbtx螖-尾 disrupts liposomes, and exhibited entomotoxic effects similar to the whole peptide, suggesting that the 尾-hairpin motif is not a determinant of these biological activities; 2) both Jbtx C-ter and Jbtx N-ter disrupted liposomes, the C-terminal peptide being the most active; and 3) while Jbtx N-ter persisted to be biologically active, Jbtx C-ter was less active when tested on different insect preparations. Molecular modeling and dynamics were applied to the urease-derived peptides to complement the structure-function analysis.
The N-terminal portion of the Jbtx carries the most important entomotoxic domain which is fully active in the absence of the 尾-hairpin motif. Although the 尾-hairpin contributes to some extent, probably by interaction with insect membranes, it is not essential for the entomotoxic properties of Jbtx.
Jbtx represents a new type of insecticidal and membrane-active peptide.