How Does Melittin Permeabilize Membranes?

Fifty years ago, the sequence of melittin, the archetypal membrane-permeabilizing peptide, was first determined (1). Soon after, the basic biophysical principles of its activity in membranes were understood. Melittin, which is the major component of Honey Bee venom, partitions strongly into membranes and, by virtue of its structural amphipathicity, disrupts the normally strict segregation between the polar and nonpolar parts of the lipid bilayer and its surroundings, enabling passage of ions, water, small molecules, and, sometimes, macromolecules.

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