title: Similarities in melittin functional group reactivities during self-association and association with lipid bilayers.
abstract: Competitive labeling of melittin over a range of concentrations in the presence and absence of liposomes provides a series of "snapshots" of the chemical reactivities of melittin's intrinsic nucleophiles. Distinct trends in apparent reactivities were observed for the Gly-1 alpha-amino group and the epsilon-amino groups of Lys-7 and Lys-21 and -23, over a range of concentrations, providing evidence for different forms of associated melittin in solution. The monomer-tetramer transition can be followed, in accord with structural details derived from X-ray crystallography. The reactivity behavior of the alpha-amino group of Gly-1 and the epsilon-amino groups of Lys-21 and Lys-23 suggests these groups undergo similar perturbations in their microenvironments during the monomer-tetramer transition in free solution. Similar changes in reactivity behavior occur upon association of melittin monomers with bilayer-forming lipids. Together, these findings suggest that the local environments of the N- and C-terminal segments have similar physicochemical properties in both the solution tetramer and the lipid-associated complex. The concentration dependence of the chemical properties of melittin is correlated with surface accessibility calculations which are used to provide a framework for interpretation. Aspects of several previously proposed models of membrane lysis can be accounted for by concentration-dependent properties of melittin.
authors.affiliation: Connaught Centre for Biotechnology Research, Willowdale, Ontario, Canada.
authors.forename: R P
authors.initials: RP
authors.lastname: Oomen
authors.forename: H
authors.initials: H
authors.lastname: Kaplan
mesh_terms: D000595:Amino Acid Sequence; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D004139:Dinitrofluorobenzene / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D046911:Macromolecular Substances; D008555:Melitten / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010449:Peptide Mapping; D012996:Solutions
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D046911:Macromolecular Substances; D012996:Solutions; D008555:Melitten; D004139:Dinitrofluorobenzene; D008239:Lysine