Conformational change and self association of monomeric melittin

Abstract

Melittin is a well-known amphipathic peptide which acts as a direct lytic factor on biological membranes [ 11. Its ability to induce leakage both on natural membranes and liposomes has been clearly demonstrated [2]. Melittin-phospholipid interactions have also been extensively studied [3-51, however few studies have been dealing with the structure of the peptide itself, in solution. It is known to behave as a tetramer [ 1,6]; it is also assumed from an early circular dichroism study [7] to be mainly in random coil. The possibility of conformational and aggregation changes induced by organic solvent or phospholipids was pointed out [8,9] but no definite experimental proof was presented on these problems. Here, we report the existence of melittin as a monomer and give the parameters which govern the self-association of the peptide. We also present arguments indicating that the polymerization process involves important changes in the secondary structure of melittin. These findings allow a more coherent picture of the behaviour of the peptide in solution.