Determination of the secondary structure of selected melittin analogues with different haemolytic activities.
In earlier studies, we have reported that minor modifications in the amino acid sequence of melittin result in dramatic changes in its biological activity. In the current study, we have investigated the secondary structure of melittin analogues with either increased or decreased haemolytic activity in order to further our understanding of the structural features involved in the binding and/or insertion of peptides into a phospholipid membrane from solution. This was accomplished by analysing the c.d. spectra of the analogues in solutions of various ionic strength and, separately, in the presence of micelles. These studies permit the assessment of the effect of small sequence modifications (i.e. single amino acid omission or substitution) on the self-association-induced secondary structure of melittin in aqueous solution, as well as its binding affinity to micelles. It was found that amphipathicity, as well as interchain distances and the orientation of hydrophobic residues, were involved in the induction of stabilized structures.
Pérez-Payá
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Torrey Pines Institute for Molecular Studies, San Diego, CA 92121.
Houghten
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RA
Blondelle
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D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D006461:Hemolysis; D006801:Humans; D008555:Melitten / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D017433:Protein Structure, Secondary; D012965:Sodium Chloride / Q000494:pharmacology
D010455:Peptides; D008555:Melitten; D012965:Sodium Chloride