Novel excitatory Conus peptides define a new conotoxin superfamily
Novel excitatory Conus peptides define a new conotoxin superfamily
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DOI：
10.1046/j.1471-4159.2003.01685.x
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发表时间：
2003-05-01
影响因子：
4.7
通讯作者：
Olivera, BM
中科院分区：
文献类型：
--
作者：
Jimenez, EC;Shetty, RP;Olivera, BM
芋螺毒素I超家族是一类新的芋螺多肽，其特征在于使用生化，电生理和分子遗传学方法。这个超家族中的肽具有八个Cys残基的新模式。五个肽，引起兴奋性神经病学，r11 a，r11 b，r11 c，r11 d和r11 e，纯化芋螺毒液;四个两栖动物外周轴突进行了测试，并显示引起重复动作电位，与成员的“雷击阴谋”的毒素，即时固定的鱼类猎物。对芋螺cDNA克隆的平行分析揭示了一类新的芋螺毒素基因，该基因在辐射芋螺毒管文库中特别富集（具有18个鉴定的旁系同源物）; radiatus克隆编码的兴奋性肽直接从毒液的特点。一个芋螺物种内相关的I-超家族肽的显着多样性是前所未有的。当与外周电路上观察到的兴奋作用相结合时，这种意想不到的多样性表明外周轴突中靶向信号传导组分的相应分子复杂性; I-芋螺毒素超家族应该为解剖和理解这些提供丰富的药理学工具矿脉。因此，I-超家族芋螺毒素有望为解剖轴突的分子组分提供一个重要的新技术平台。
A new class of Conus peptides, the I-superfamily of conotoxins, has been characterized using biochemical, electrophysiological and molecular genetic methods. Peptides in this superfamily have a novel pattern of eight Cys residues. Five peptides that elicited excitatory symptomatology, r11a, r11b, r11c, r11d and r11e, were purified from Conus radiatus venom; four were tested on amphibian peripheral axons and shown to elicit repetitive action potentials, consistent with being members of the 'lightning-strike cabal' of toxins that effect instant immobilization of fish prey. A parallel analysis of Conus cDNA clones revealed a new class of conotoxin genes that was particularly enriched (with 18 identified paralogues) in a Conus radiatus venom duct library; several C. radiatus clones encoded the excitatory peptides directly characterized from venom. The remarkable diversity of related I-superfamily peptides within a single Conus species is unprecedented. When combined with the excitatory effects observed on peripheral circuitry, this unexpected diversity suggests a corresponding molecular complexity of the targeted signaling components in peripheral axons; the I-conotoxin superfamily should provide a rich lode of pharmacological tools for dissecting and understanding these. Thus, the I-superfamily conotoxins promise to provide a significant new technology platform for dissecting the molecular components of axons.