Generalised bilayer perturbation from peptide helix dimerisation at membrane surfaces: vesicle lysis induced by disulphide-dimerised melittin analogues

The effects of covalent dimerisation of melittin by disulphide formation in cysteine-substitution analogues, (melittin K23C)(2) and (melittin K23Q,Q25 C)(2), on the kinetics of pore formation in phosphatidylcholine small unila mellar vesicles mas measured under low ionic strength conditions, The initi al rate of melittin-induced pore formation increased with the square of the peptide concentration, whereas both disulphide-dimerised melittin analogue s showed a first-order dependence of pore formation rates on peptide concen tration. These results indicate that peptide dimerisation is rate-limiting for pore formation under these conditions, A model for a generalised bilaye r perturbation resulting from the self-association of a pair of peptide hel ices at the membrane surface is proposed which may have implications for a number of biological processes that involve the interaction of helical poly peptides with membranes. (C) 1999 Federation of European Biochemical Societ ies.