McIntosh J M, Hasson A, Spira M E, Gray W R, Li W, Marsh M, Hillyard D R, Olivera B M
Department of Biology, University of Utah, Salt Lake City 84112, USA.
J Biol Chem. 1995 Jul 14;270(28):16796-802. doi: 10.1074/jbc.270.28.16796.
Conus peptides, including omega-conotoxins and alpha-conotoxins (targeting calcium channels and nicotinic acetylcholine receptors, respectively) have been useful ligands in neuroscience. In this report, we describe a new family of sodium channel ligands, the mu-O-conotoxins. The two peptides characterized, mu-O-conotoxins MrVIA and MrVIB from Conus marmoreus potently block the sodium conductance in Aplysia neurons. This is in marked contrast to standard sodium channel blockers that are relatively ineffective in this system. The sequences of the peptides are as follows. mu-O-conotoxin MrVIA: ACRKKWEYCIVPIIGFIYCCPGLICGPFVCV mu-O-conotoxin MrVIB: ACSKKWEYCIVPILGFVYCCPGLICGPFVCV mu-O-conotoxin MrVIA was chemically synthesized and proved indistinguishable from the natural product. Surprisingly, the mu-O-conotoxins show no sequence similarity to the mu-O-conotoxins. However, ananalysis of cDNA clones encoding the mu-O-conotoxin MrVIB demonstrated striking sequence similarity to omega- and delta-conotoxin precursors. Together, the omega-, delta-, and mu-O-conotoxins define the O-superfamily of Conus peptides. The probable biological role and evolutionary affinities of these peptides are discussed.
芋螺肽，包括ω-芋螺毒素和α-芋螺毒素（分别作用于钙通道和烟碱型乙酰胆碱受体），在神经科学领域一直是有用的配体。在本报告中，我们描述了一个新的钠通道配体家族——μ-O-芋螺毒素。已鉴定的两种肽，来自大理石芋螺的μ-O-芋螺毒素MrVIA和MrVIB，能有效阻断海兔神经元中的钠电导。这与在该系统中相对无效的标准钠通道阻滞剂形成了显著对比。这些肽的序列如下：μ-O-芋螺毒素MrVIA：ACRKKWEYCIVPIIGFIYCCPGLICGPFVCV；μ-O-芋螺毒素MrVIB：ACSKKWEYCIVPILGFVYCCPGLICGPFVCV。μ-O-芋螺毒素MrVIA经化学合成，证明与天然产物无异。令人惊讶的是，μ-O-芋螺毒素与μ-O-芋螺毒素没有序列相似性。然而，对编码μ-O-芋螺毒素MrVIB的cDNA克隆进行分析，发现其与ω-芋螺毒素和δ-芋螺毒素前体具有显著的序列相似性。ω-芋螺毒素、δ-芋螺毒素和μ-O-芋螺毒素共同定义了芋螺肽的O超家族。本文还讨论了这些肽可能的生物学作用和进化亲缘关系。
