J Biol Chem, 2011 Nov 29
Bee venom antimicrobial peptide, melittin, besides showing versatile activity against microorganisms neutralizes lipopolysaccharide (LPS)-induced pro-inflammatory responses in macrophage cells.
However, how the amino acid sequence of melittin contributes in its anti-inflammatory properties is mostly unknown. To determine the importance of the leucine zipper sequence of melittin in its neutralization of LPS-induced inflammatory responses in macrophages and interaction with LPS, anti-inflammatory properties of melittin and its three analogues and their interactions with LPS were studied in detail.
Two of these analogues namely, melittin Mut-1 (MM-1) and melittin Mut-2 (MM-2) possess leucine to alanine substitutions in the single and double heptadic leucine residue(s) of melittin respectively while the third analogue is a scrambled peptide (Mel-SCR) which contains the amino acid composition of melittin with minor rearrangement in its leucine zipper sequence.
Though MM-1 partly inhibited the production of pro-inflammatory cytokines in RAW 264.7 and rat primary macrophage cells in the presence of LPS, MM-2 and Mel-SCR were negligibly active. A progressive decrease in interaction of melittin with LPS, aggregation in LPS and dissociation of LPS aggregates with alteration in the leucine zipper sequence of melittin was observed.
Further, with alteration in the leucine zipper sequence of melittin, these analogues failed to exhibit cellular responses that are associated with neutralization of LPS-induced inflammatory responses in macrophage cells by melittin.
The data indicated a probable important role of the leucine zipper sequence of melittin in neutralizing LPS-induced pro-inflammatory responses in macrophage cells as well as in its interaction with LPS…
Though further studies are required in understanding the role of this motif in these molecules, the data probably indicate that one can design anti-LPS or LPS-binding molecule based on this structural element.
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