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靶向离子通道的神经毒素起源于抗微生物防御肽

朱丽梅, 高斌, 朱顺义^*

中国科学院动物研究所，农业虫害鼠害综合治理研究国家重点实验室，多肽生物学及进化研究组，北京 100101

摘要

靶向离子通道的神经毒素和抗微生物防御肽(defensin)享有三个共同的蛋白折叠(fold)类型，即半胱氨酸稳定的α-螺旋和β-片层折叠(cysteine-stabilized α-helix and β-sheet, CSαβ)，抑制剂胱氨酸结折叠(inhibitor cystine knot, ICK)和β-防御肽折叠(β-defensin, BDF)。序列、结构和功能等多维证据显示靶向离子通道的神经毒素起源于相关的古老防御肽。毒素和防御肽系统正在成为研究保守结构支架功能新颖化(neofunctionalization)进化机制的理想体系。阐明蛋白质功能新颖化的进化机制不仅有利于回答进化生物学的基本科学问题，而且对于合理的药物设计具有重要的指导意义。本文综合阐述了神经毒素起源于抗微生物防御肽方面的最新研究进展。

关键词： 功能新颖化; 半胱氨酸稳定的α-螺旋和β-片层折叠; 抑制剂胱氨酸结折叠; β-防御肽折叠; 离子通道

分类号：Q594;Q951;R97

Origin of neurotoxins from defensins

ZHU Li-Mei, GAO Bin, ZHU Shun-Yi^*

Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

Abstract

There are at least three conserved protein folds shared by ion channel-targeted neurotoxins and antimicrobial defensins, including cysteine-stabilized α-helix and β-sheet fold (CSαβ), inhibitor cystine knot fold (ICK) and β-defensin fold (BDF). Based on a combined data of sequences, structures and functions, it has been proposed that these neurotoxins could originate from related ancient antimicrobial defensins by neofunctionalization. This provides an ideal system to study how a novel function emerged from a conserved structural scaffold during evolution. The elucidation of functional novelty of proteins not only has great significance in evolutionary biology but also will be helpful in guiding rational molecular design. This review describes recent progresses in origin of neurotoxins, focusing on the three conserved protein scaffolds.

Key words: neofunctionalization; cysteine stabilized α-helical and β-sheet fold; inhibitor cystine knot fold; β-defensin fold; ion channel

收稿日期：2014-06-13　　录用日期：2014-08-22

通讯作者：朱顺义　　E-mail: zhusy@ioz.ac.cn

引用本文：

朱丽梅, 高斌, 朱顺义. 靶向离子通道的神经毒素起源于抗微生物防御肽[J]. 生理学报 2015; 67 (3): 239-247.

ZHU Li-Mei, GAO Bin, ZHU Shun-Yi. Origin of neurotoxins from defensins. Acta Physiol Sin 2015; 67 (3): 239-247 (in Chinese with English abstract).