Interaction and lipid-induced conformation of two cecropin-melittin hybrid peptides depend on peptide and membrane composition.
The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-9)] with liposomes was studied by differential scanning calorimetry (DSC), circular dichroism (CD), and quasi-elastic light scattering (QELS). The study was carried out with large unilamellar vesicles (LUVs) of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a binary mixture of DMPC/DMPG, in a wide range of peptide-to-lipid (P:L) molar ratios (0 to 1:7). DSC results indicate that, for both peptides, the interaction depends on membrane composition, with very different behavior for zwitterionic and anionic membranes. CD data show that, although the two peptides have different secondary structures in buffer (random coil for CA(1-7)M(2-9) and predominantly beta-sheet for CA(1-8)M(1-18)), they both adopt an alpha-helical structure in the presence of the membranes. Overall, results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, which gives place to aggregation in the gel phase and precipitation after a threshold peptide concentration. In the case of zwitterionic membranes, a progressive surface coverage with peptide molecules destabilizes the membrane, eventually leading to membrane disruption. Moreover, delicate modulations in behavior were observed depending on the peptide.
Abrunhosa
Filipa
F
CIQ (U.P.) Department of Chemistry, Faculty of Sciences, University of Porto, P-4169-007 Porto, Portugal.
Faria
Sílvia
S
Gomes
Paula
P
Tomaz
Isabel
I
Pessoa
João C
JC
Andreu
David
D
Bastos
Margarida
M
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D008027:Light; D008055:Lipids / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D012542:Scattering, Radiation
D023181:Antimicrobial Cationic Peptides; D008055:Lipids; D010455:Peptides; D008555:Melitten; C031161:cecropin A