Tomita M, Takase M, Wakabayashi H, Bellamy W
Nutritional Science Laboratory, Morinaga Milk Industry Co. Ltd., Kanagawa, Japan.
Adv Exp Med Biol. 1994;357:209-18. doi: 10.1007/978-1-4615-2548-6_20.
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.
乳铁蛋白在其N端附近发现含有一个抗菌序列，该序列的作用机制似乎与铁螯合不同。在对人乳铁蛋白和牛乳铁蛋白进行胃蛋白酶切割后，分离出了代表该结构域的抗菌肽。发现该抗菌序列主要由一个18个氨基酸残基的环组成，该环由人乳铁蛋白的第20和37位半胱氨酸残基之间的二硫键形成，或由牛乳铁蛋白的第19和36位半胱氨酸残基之间的二硫键形成。鉴定出的结构域含有高比例的碱性残基，与已知靶向微生物膜的其他各种抗菌肽一样，它似乎位于折叠蛋白的表面，使其能够与微生物细胞的表面成分相互作用。分离出的结构域“乳铁蛋白”具有强大的广谱抗菌特性，其作用具有致死性，会导致菌落形成能力迅速丧失。这些证据表明，该结构域是乳铁蛋白杀菌特性的结构区域。证据还表明，乳铁蛋白经酶消化产生的活性肽可能有助于宿主抵御微生物疾病。
