Antimicrobial peptides of lactoferrin.
Lactoferrin was found to contain an antimicrobial sequence near its N-terminus which appears to function by a mechanism distinct from iron chelation. Antimicrobial peptides representing this domain were isolated following pepsin cleavage of human lactoferrin and bovine lactoferrin. The antimicrobial sequence was found to consist mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin. The identified domain contains a high proportion of basic residues, like various other antimicrobial peptides known to target microbial membranes and it appears to be located on the surface of the folded protein allowing its interaction with surface components of microbial cells. The isolated domain, "lactoferrin", was shown to have potent broad spectrum antimicrobial properties and its effect was lethal causing a rapid loss of colony-forming capability. Such evidence points to the conclusion that this domain is the structural region responsible for the microbicidal properties of lactoferrin. The evidence also suggests the possibility that active peptides produced by enzymatic digestion of lactoferrin may contribute to the host defense against microbial disease.
Tomita
M
M
Nutritional Science Laboratory, Morinaga Milk Industry Co. Ltd., Kanagawa, Japan.
Takase
M
M
Wakabayashi
H
H
Bellamy
W
W
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D001059:Apoproteins / Q000737:chemistry; D001419:Bacteria / Q000187:drug effects*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases; D005260:Female; D005658:Fungi / Q000187:drug effects*; D005766:Gastrointestinal Contents / Q000382:microbiology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D007781:Lactoferrin / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001059:Apoproteins; D010446:Peptide Fragments; C039223:apolactoferrin; D010450:Endopeptidases; D007781:Lactoferrin