Interaction of a synthetic peptide based on the neutrophil-derived antimicrobial protein CAP37 with dipalmitoyl-phosphatidylcholine membranes.
CAP37, a cationic antimicrobial protein of Mr 37 kDa is constitutively expressed in human neutrophils. A synthetic peptide, CAP37 P20-44, corresponding to amino acid residues 20 through 44 of the native CAP37 molecule has been shown to mimic the antimicrobial activity of the native protein. An analog of peptide CAP37 P20-44 was synthesized in which the cysteine residues at positions 26 and 42 were replaced with serine residues (CAP37 P20-44Ser). This resulted in a peptide that no longer exhibited bactericidal activity. The effect of different concentrations of the active CAP37 peptide, CAP37 P20-44, and its inactive analog, CAP37 P20-44Ser, on artificial lipid membranes composed of dipalmitoyl phosphatidylcholine (DPPC) was studied using small-angle X-ray scattering and differential scanning calorimetry. The results indicated that CAP37 P20-44 perturbs the periodicity of the lamellar structure as shown by small angle X-ray diffraction, while the effect of the inactive peptide is not as strong. Differential scanning calorimetry further confirms that CAP37 P20-44 interacts with lipid membranes as indicated by increased width of the transition and decreased peak height. Moreover, it completely abolishes the pretransition temperature of the DPPC membranes. The effect of the inactive peptide, CAP37 P20-44Ser on the thermotropic properties of DPPC was small. These studies suggest that CAP37 perturbs the lamellar structure of lipid bilayers and further suggests that the antibiotic action of the molecule may be through its interactions with the lipid components of the Gram negative bacterial membrane.
Polikandritou Lambros
M
M
College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Sheu
E
E
Lin
J S
JS
Pereira
H A
HA
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002352:Carrier Proteins; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D013816:Thermodynamics; D014961:X-Ray Diffraction
C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D008081:Liposomes; D010446:Peptide Fragments; D015060:1,2-Dipalmitoylphosphatidylcholine