Melittin amphipathic structures

Figure 8.6 MeLittin-induced membrane fusion-fragmentation process as followed by NMR. The amphipathic melittin 3D structure was obtained from the PDB using the ViewerLite software. Adapted from Dufourc et al. (1986) and Pott and Dufourc (1995). The vesicle drawing is courtesy of...

Melittin, which is an amphipathic peptide from honeybee venom, consists of 26 amino acid residues and adopts different conformations from a random coil, to an a-helix, and to a self-assembled tetramer under certain aqueous environments see Fig. 9. We have carried out our systematic studies of the hydration dynamics in these three conformations using a single intrinsic tryptophan ( W19) as a molecular probe. The folded a-helix melittin was formed with lipid interactions to mimic physiological membrane-bound conditions. The self-assembled tetramer was prepared under high-salt concentration (NaCl = 2 M). The tryptophan emission of three structures under three different aqueous environments is 348.5 nm, 341 nm, and 333.5 nm, which represents different exposures of aqueous solution from complete in random-coil, to locating at the lipid surface of a nanochannel (50 A in diameter) in a-helix and to partially buried in tetramer. Figure 10 shows... 

Although both melittin and the cecropins share a structural motif that consists of two helices linked by a hinge region, the polarity of the helices is reversed in that melittin has a hydrophobic N-terminus and an amphipathic C-terminus the converse is true for the cecropins. The relationship of structural difference to the different activities of these two peptides was probed by preparation of shortened cecropin-melittin hybrids (200, 201) that show enhanced antibacterial activity and decreased hemolytic effects. 

The second major structural class studied is the O-helical class. Interestingly, such structures tend to be rather disorganized in aqueous solution, but they become a-helical structured upon entering a membrane environment or exposure to nonpolar solvents (89,90). The predominant structures observed upon interaction with membranes are helix-bend-helix with a 9-16 amino acid amphipathic a-helix, a 2-4 residue bend, and a 11-14 amino acid amphipathic but more hydrophobic a-helix, as demonstrated by two-dimensional NMR of cecropins A and B, melittin, the magainins, and a synthetic cecropin-melittin hybrid (89,91-93). A small variation is provided by mammalian cecropin Pi, which comprises an uninterrupted amphiphilic helix for 24 amino acids, bounded by 2-4 residues at the N- and C-termini. 

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