Huang Feijuan, Du Weihong
Department of Chemistry, Renmin University of China, 59 Zhong Guan Cun Street, Beijing 100872, PR China.
Toxicon. 2009 Aug;54(2):153-60. doi: 10.1016/j.toxicon.2009.03.033. Epub 2009 Apr 16.
Conotoxins are mainly disulfide-rich short peptides active on different ion channels, neurotransmitter receptors or transporters in nervous system, exhibiting highly diversified composition, structures and biological functions. Besides these kinds of conopeptides, some novel cysteine-free conopeptides have also been reported. Conomarphin, a cystine-free 15-residue conopeptide from Conus marmoreus, has been purified and classified into M-superfamily. In addition to its unique characteristic of a D-type phenylalanine at the third residue from the C-terminus, conomarphin has an unusual hydroxyproline residue at position 10. To make an effort to understand the role of hydroxyproline post-translational modification in conomarphin, (1)H NMR solution structure of Hyp10Pro variant of conomarphin was resolved and compared with the native conomarphin in the present work. The Hyp10Pro conomarphin has a type II-beta-turn near the C-terminus instead of a 3(10) helix in native conomarphin. The compact loop region in native conomarphin becomes more open when hydroxyproline is displaced by proline. This reveals that hydroxyproline residue is essential for the structure of conomarphin just like D-Phe13. The unusual post-translational modification of conomarphin implies a unique selectivity of hydroxylation in toxin sequence.
芋螺毒素主要是富含二硫键的短肽，作用于神经系统的不同离子通道、神经递质受体或转运体，其组成、结构和生物学功能高度多样。除了这些类型的芋螺肽外，还报道了一些新型无半胱氨酸的芋螺肽。芋螺吗啡是一种来自大理石芋螺的无胱氨酸的15个残基的芋螺肽，已被纯化并归类为M超家族。除了在C端第三个残基处具有D型苯丙氨酸这一独特特征外，芋螺吗啡在第10位还有一个不寻常的羟脯氨酸残基。为了努力了解羟脯氨酸翻译后修饰在芋螺吗啡中的作用，在本研究中解析了芋螺吗啡Hyp10Pro变体的（1）H NMR溶液结构，并与天然芋螺吗啡进行了比较。Hyp10Pro芋螺吗啡在C端附近有一个II型β-转角，而不是天然芋螺吗啡中的3（10）螺旋。当羟脯氨酸被脯氨酸取代时，天然芋螺吗啡中的紧密环区域变得更加开放。这表明羟脯氨酸残基与D-Phe13一样，对芋螺吗啡的结构至关重要。芋螺吗啡不寻常的翻译后修饰意味着毒素序列中羟基化具有独特的选择性。
