Solution structure of cryptdin-4, a mouse Paneth cell α-defensin
Solution structure of cryptdin-4, a mouse Paneth cell α-defensin
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DOI：
10.1021/bi048645p
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发表时间：
2004-12-21
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：
Jing, WG;Hunter, HN;Vogel, HJ
哺乳动物防御素是丰富的抗微生物肽，有助于宿主防御。它们具有几个保守的氨基酸，包括六个不变的半胱氨酸残基，形成三个分子内二硫键并稳定三级结构。crytdin -4 （Crp4）是一种具有强效体外杀菌活性的小鼠α -防御素，其主要结构与所有已知α -防御素不同，其多肽主链在Cys（IV）和Cys(V)之间独特地缺少三个残基。核磁共振扩散实验表明，Crp4在溶液中为单体，通过二维质子核磁共振确定其三维溶液结构为三链反平行β -片，β -链通过一系列紧密旋转和β -发夹连接在一起。然而，Crp4中β -sheet的总体含量低于其他α -防御素结构，而Crp4 β -发夹的形状和方向也不同于其他α -防御素结构。这些结构特征加上Crp4的高总阳离子性可能有助于其广泛的杀菌谱和膜破坏活性。
Mammalian defensins are abundant antimicrobial peptides that contribute to host defense. They are characterized by several conserved amino acids, including six invariant cysteine residues which form three intramolecular disulfide bonds and stabilize the tertiary structure. Cryptdin-4 (Crp4), a mouse alpha-defensin with potent in vitro bactericidal activity, has a primary structure distinct from all known alpha-defensins in that its polypeptide backbone uniquely lacks three residues between Cys(IV) and Cys(V). NMR diffusion experiments showed that Crp4 is monomeric in solution, and its three-dimensional solution structure, determined by two-dimensional proton NMR, consists of a triple-stranded antiparallel beta-sheet with the beta-strands joined to each other by a series of tight turns and a beta-hairpin. However, the overall beta-sheet content in Crp4 is lower than that of other alpha-defensin structures, while the shape and orientation of the Crp4 beta-hairpin also differ from those of other alpha-defensin structures. These structural characteristics combined with the high overall cationicity of Crp4 may contribute to its broad bactericidal spectrum and membrane disruptive activity.