Maculatin 1.1, an anti-microbial peptide from the Australian tree frog, Litoria genimaculata - Solution structure and biological activity

The dorsal glands of Australian tree frogs from the Litoria species contain a diversity of antibiotic peptides that forms part of the defence system o f the animal. Here, the antibiotic activity and structure of maculatin 1.1, a 21 amino acid peptide from Litoria genimaculata, are compared. The activ ity data on maculatin 1.1 and a series of its analogues imply that the mech anism of action of maculatin 1.1 involves binding to, and subsequent lysis of, the bacterial cell membrane. The structure of maculatin 1.1 was determi ned using NMR spectroscopy in a trifluoroethanol/water mixture and when inc orporated into dodecylphosphocholine micelles. Under both conditions, the p eptide adopts a very similar conformation, i.e. a helical structure with a central kink in the vicinity of Pro15. The kink allows the peptide to adopt a well-defined amphipathic conformation along its entire length. The simil ar structures determined under both solvent conditions imply that structure s of membrane-interacting peptides in trifluoroethanol/water mixtures are r epresentative of those adopted in a membrane environment, e.g. when incorpo rated into micelles. The synthetic Ala15 analogue of maculatin 1.1 has mark edly reduced activity and its NMR-derived structure is a well-defined helix , which lacks the central kink and flexibility of the parent molecule. It i s concluded that the kink is important for full biological activity of the peptide, probably because it allows maximum amphipathicity of the peptide t o facilitate interaction with the membrane. The structure of maculatin 1.1 is compared with a related peptide, caerin 1.1 [Wong, H., Bowie, J.H. and C arver, J.A. (1997) Eur. J. Biochem. 247, 545-557], which has an additional central proline residue and enhanced central flexibility compared with macu latin 1.1. The role of central flexibility within antibiotic peptides in th eir interaction with bacterial membranes is discussed.