Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin
Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin
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DOI：
10.1021/bi972323m
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发表时间：
1998-03-24
期刊：
影响因子：
2.9
通讯作者：
Vogel, HJ
中科院分区：
文献类型：
--
作者：
Hwang, PM;Zhou, N;Vogel, HJ
牛乳铁蛋白（LfcinB）是由胃蛋白酶裂解乳铁蛋白（Lactoferrin）而产生的25个氨基酸残基的抗菌肽，是一种具有多种免疫学功能的80 kDa铁结合糖蛋白。LfcinB的NMR结构揭示了有点扭曲的反平行β-折叠。这与牛乳铁蛋白的X射线结构形成对比，其中（LfcinB的）残基1-13形成α-螺旋。因此，乳铁蛋白B的这一区域似乎能够采用螺旋或片状构象，类似于已提出的淀粉样蛋白原朊病毒蛋白和阿尔茨海默氏β-肽。LfcinB具有由残基Phe 1、Cys 3、Trp 6、Trp 8、Pro 16、Ile 18和Cys 20组成的延伸的疏水表面。这些残基的侧链在NMR结构中明确定义。许多亲水性和带正电荷的残基围绕疏水表面，赋予LfcinB两亲性特征，LfcinB与大量通过膜破坏发挥其抗微生物活性的阳离子肽具有许多相似性。许多这些肽的结构已得到很好的表征，并提出了其膜透化机制的模型。LfcinB的NMR溶液结构可能比完整乳铁蛋白的X-射线结构所建议的与膜相互作用更相关。基于溶液结构，现在可以提出LfcinB抗菌作用的潜在机制。
The solution structure of bovine lactoferricin (LfcinB) has been determined using 2D H-1 NMR spectroscopy, LfcinB is a 25-residue antimicrobial peptide released by pepsin cleavage of lactoferrin, an 80 kDa iron-binding glycoprotein with many immunologically important functions. The NMR structure of LfcinB reveals a somewhat distorted antiparallel beta-sheet. This contrasts with the X-ray structure of bovine lactoferrin, in which residues 1-13 (of LfcinB) form an alpha-helix. Hence, this region of lactoferricin B appears able to adopt a helical or sheetlike conformation, similar to what has been proposed for the amyloidogenic prion proteins and Alzheimer's beta-peptides. LfcinB has an extended hydrophobic surface comprised of residues Phe1, Cys3, Trp6, Trp8, Pro16, Ile18, and Cys20. The side chains of these residues are well-defined in the NMR structure. Many hydrophilic and positively charged residues surround the hydrophobic surface, giving LfcinB an amphipathic character, LfcinB bears numerous similarities to a vast number of cationic peptides which exert their antimicrobial activities through membrane disruption. The structures of many of these peptides have been well characterized, and models of their membrane-permeabilizing mechanisms have been proposed. The NMR solution structure of LfcinB may be more relevant to membrane interaction than that suggested by the X-ray structure of intact lactoferrin. Based on the solution structure, it is now possible to propose potential mechanisms for the antimicrobial action of LfcinB.