Characterization of Maximin 3 Structure and Membrane Leakage

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Maximin 3 is a 27 amino acid cationic antimicrobial peptide that is derived from the skin secretions of the toad Bombina maxima. Maximin 3 has strong activity against a variety of bacteria (Gram-positive and Gram-negative), fungi, and viruses and is thought to cause toxicity by interaction with the plasma membrane. We previously quantified the binding affinity of Maximin 3 for lipid vesicles that mimic both bacterial and mammalian membranes and found that the peptide interacts more strongly with bacterial than mammalian models, in part due to the negative charge of these membranes.In our current work we used Forster resonance energy transfer (FRET) and fluorescence leakage assays to further characterize this interaction. Specifically, we found that the end-to-end distance of the peptide as determined by FRET is consistent with an extended α-helical conformation, both in solution and when bound to bacterial and mammalian model membranes. Under the same experimental conditions, we found that Maximin 3 is capable of inducing leakage of rhodamine from vesicles that mimic bacterial membranes. These results are consistent with the hypothesis that the mechanism of Maximin 3 toxicity towards bacteria is due to a direct interaction between Maximin 3 and the outer or inner bacterial membrane. We further suggest that Maximin 3 adopts an extended α-helical conformation in the leakage-inducing state, though it is not yet clear if the peptide is monomeric or oligomeric under these conditions.