Vogel Hans J, Schibli David J, Jing Weiguo, Lohmeier-Vogel Elke M, Epand Raquel F, Epand Richard M
Department of Biological Sciences, University of Calgary, AB, Canada.
Biochem Cell Biol. 2002;80(1):49-63. doi: 10.1139/o01-213.
The iron-binding protein lactoferrin is a multifunctional protein that has antibacterial, antifungal, antiviral, antitumour, anti-inflammatory, and immunoregulatory properties. All of these additional properties appear to be related to its highly basic N-terminal region. This part of the protein can be released in the stomach by pepsin cleavage at acid pH. The 25-residue antimicrobial peptide that is released is called lactoferricin. In this work, we review our knowledge about the structure of the peptide and attempt to relate this to its many functions. Microcalorimetry and fluorescence spectroscopy data regarding the interaction of the peptide with model membranes show that binding to net negatively charged bacterial and cancer cell membranes is preferred over neutral eukaryotic membranes. Binding of the peptide destabilizes the regular membrane bilayer structure. Residues that are of particular importance for the activity of lactoferricin are tryptophan and arginine. These two amino acids are also prevalent in "penetratins", which are regions of proteins or synthetic peptides that can spontaneously cross membranes and in short hexapeptide antimicrobial peptides derived through combinatorial chemistry. While the antimicrobial, antifungal, antitumour, and antiviral properties of lactoferricin can be related to the Trp/Arg-rich portion of the peptide, we suggest that the anti-inflammatory and immunomodulating properties are more related to a positively charged region of the molecule, which, like the alpha- and beta-defensins, may act as a chemokine. Few small peptides are involved in as wide a range of host defense functions as bovine and human lactoferricin.
铁结合蛋白乳铁蛋白是一种多功能蛋白，具有抗菌、抗真菌、抗病毒、抗肿瘤、抗炎和免疫调节特性。所有这些附加特性似乎都与其高度碱性的N端区域有关。该蛋白的这一部分在酸性pH条件下可被胃蛋白酶在胃中切割释放出来。释放出的由25个氨基酸残基组成的抗菌肽称为乳铁蛋白肽。在这项工作中，我们回顾了关于该肽结构的知识，并试图将其与多种功能联系起来。关于该肽与模型膜相互作用的微量热法和荧光光谱数据表明，与带净负电荷的细菌和癌细胞膜结合优于与中性真核细胞膜结合。该肽的结合会破坏规则的膜双层结构。对乳铁蛋白肽活性特别重要的残基是色氨酸和精氨酸。这两种氨基酸在“穿膜肽”中也很常见，穿膜肽是蛋白质或合成肽中能够自发穿过膜的区域，以及通过组合化学衍生的短六肽抗菌肽中也有。虽然乳铁蛋白肽的抗菌、抗真菌、抗肿瘤和抗病毒特性可能与其富含色氨酸/精氨酸的部分有关，但我们认为其抗炎和免疫调节特性更与分子的带正电荷区域有关，该区域与α-和β-防御素一样，可能作为一种趋化因子发挥作用。很少有小肽像牛和人乳铁蛋白肽那样参与如此广泛的宿主防御功能。
