Teichert Russell W, Rivier Jean, Dykert John, Cervini Laura, Gulyas Jozsef, Bulaj Grzegorz, Ellison Michael, Olivera Baldomero M
Department of Biology, University of Utah, 254 South 1400 East, Salt Lake City, UT 84112, USA.
Toxicon. 2004 Aug;44(2):207-14. doi: 10.1016/j.toxicon.2004.05.026.
The venoms of cone snails are rich in multiply disulfide-crosslinked peptides, the conotoxins. Conotoxins are grouped into families on the basis of shared cysteine patterns and homologous molecular targets. For example, both the kappaA- and alphaA-conotoxin families share the same Class IV Cys pattern (-CC-C-C-C-C-), but differ in their molecular targets. The kappaA-conotoxins are excitatory toxins that purportedly block potassium channels, while the alphaA-conotoxins are paralytic conotoxins that inhibit nicotinic acetylcholine receptors (nAChRs). In this work, we describe the isolation and characterization of a novel Conus peptide from venom milked from Hawaiian specimens of Conus obscurus. This peptide shares the Class IV Cys pattern but differs from both previously characterized alphaA- and kappaA-conotoxins in the spacing of amino acids between Cys resides. However, the peptide is similar to previously characterized alphaA-conotoxins in its paralytic effects on fish and its antagonist activity on the neuromuscular nAChR. Unexpectedly, the peptide differs in its disulfide bonding from alphaA-conotoxin PIVA. We have named this unique peptide alphaA-conotoxin OIVA, and we consider it the defining member of a subfamily of alphaA-conotoxins that we designate the alphaA(1-3)-conotoxins to identify them by their unique disulfide bonding framework. These results indicate that the alphaA-conotoxin family is both more structurally diverse and broadly distributed than previously believed.
芋螺的毒液富含多重二硫键交联的肽类，即芋螺毒素。芋螺毒素根据共享的半胱氨酸模式和同源分子靶点被分为不同家族。例如，κA-芋螺毒素家族和αA-芋螺毒素家族都具有相同的IV类半胱氨酸模式（-CC-C-C-C-C-），但它们的分子靶点不同。κA-芋螺毒素是兴奋性毒素，据称可阻断钾通道，而αA-芋螺毒素是麻痹性芋螺毒素，可抑制烟碱型乙酰胆碱受体（nAChRs）。在这项研究中，我们描述了从夏威夷暗芋螺标本采集的毒液中分离和鉴定出一种新型芋螺肽。这种肽具有IV类半胱氨酸模式，但在半胱氨酸残基之间的氨基酸间距上与先前鉴定的αA-和κA-芋螺毒素均不同。然而，该肽在对鱼类的麻痹作用及其对神经肌肉nAChR的拮抗活性方面与先前鉴定的αA-芋螺毒素相似。出乎意料的是，该肽的二硫键与αA-芋螺毒素PIVA不同。我们将这种独特的肽命名为αA-芋螺毒素OIVA，并认为它是αA-芋螺毒素一个亚家族的定义成员，我们将该亚家族指定为αA(1-3)-芋螺毒素，以便通过其独特的二硫键框架来识别它们。这些结果表明，αA-芋螺毒素家族在结构上比以前认为的更加多样化且分布更广泛。
