Haney Evan F, Nazmi Kamran, Lau Fanny, Bolscher Jan G M, Vogel Hans J
Structural Biology Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4.
Biochimie. 2009 Jan;91(1):141-54. doi: 10.1016/j.biochi.2008.04.013. Epub 2008 May 15.
Human lactoferrampin is a novel antimicrobial peptide found in the cationic N-terminal lobe of the iron-binding human lactoferrin protein. The amino acid sequence that directly corresponds to the previously characterized bovine lactoferrin-derived lactoferrampin peptide is inactive on its own (WNLLRQAQEKFGKDKSP, residues 269-285). However, by increasing the net positive charge near the C-terminal end of human lactoferrampin, a significant increase in its antibacterial and Candidacidal activity was obtained. Conversely, the addition of an N-terminal helix cap (sequence DAI) did not have any appreciable effect on the antibacterial or antifungal activity of human lactoferrampin peptides, even though it markedly influenced that of bovine lactoferrampin. The solution structure of five human lactoferrampin variants was determined in SDS micelles and all of the structures display a well-defined amphipathic N-terminal helix and a flexible cationic C-terminus. Differential scanning calorimetry studies indicate that this peptide is capable of inserting into the hydrophobic core of a membrane, while fluorescence spectroscopy results suggest that a hydrophobic patch encompassing the single Trp and Phe residues as well as Leu, Ile and Ala side chains mediates the interaction between the peptide and the hydrophobic core of a phospholipid bilayer.
人乳铁杀菌肽是一种新型抗菌肽，存在于结合铁的人乳铁蛋白的阳离子N末端叶中。与先前表征的源自牛乳铁蛋白的乳铁杀菌肽直接对应的氨基酸序列本身无活性（WNLLRQAQEKFGKDKSP，第269 - 285位残基）。然而，通过增加人乳铁杀菌肽C末端附近的净正电荷，其抗菌和抗念珠菌活性显著增加。相反，添加N末端螺旋帽（序列DAI）对人乳铁杀菌肽的抗菌或抗真菌活性没有任何明显影响，尽管它对牛乳铁杀菌肽的活性有显著影响。在SDS胶束中测定了五种人乳铁杀菌肽变体的溶液结构，所有结构均显示出明确的两亲性N末端螺旋和灵活的阳离子C末端。差示扫描量热法研究表明，该肽能够插入膜的疏水核心，而荧光光谱结果表明，包含单个色氨酸和苯丙氨酸残基以及亮氨酸、异亮氨酸和丙氨酸侧链的疏水区域介导了该肽与磷脂双层疏水核心之间的相互作用。
