Bayrhuber Monika, Vijayan Vinesh, Ferber Michael, Graf Roland, Korukottu Jegannath, Imperial Julita, Garrett James E, Olivera Baldomero M, Terlau Heinrich, Zweckstetter Markus, Becker Stefan
Department for NMR-based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
J Biol Chem. 2005 Jun 24;280(25):23766-70. doi: 10.1074/jbc.C500064200. Epub 2005 Apr 15.
Conkunitzin-S1 (Conk-S1) is a 60-residue neurotoxin from the venom of the cone snail Conus striatus that interacts with voltage-gated potassium channels. Conk-S1 shares sequence homology with Kunitz-type proteins but contains only two out of the three highly conserved cysteine bridges, which are typically found in these small, basic protein modules. In this study the three-dimensional structure of Conk-S1 has been solved by multidimensional NMR spectroscopy. The solution structure of recombinant Conk-S1 shows that a Kunitz fold is present, even though one of the highly conserved disulfide cross-links is missing. Introduction of a third, homologous disulfide bond into Conk-S1 results in a functional toxin with similar affinity for Shaker potassium channels. The affinity of Conk-S1 can be enhanced by a pore mutation within the Shaker channel pore indicating an interaction of Conk-S1 with the vestibule of potassium channels.
芋螺毒素Conkunitzin-S1（Conk-S1）是一种由条纹芋螺毒液产生的含60个氨基酸残基的神经毒素，它可与电压门控钾通道相互作用。Conk-S1与库尼茨型蛋白具有序列同源性，但仅含有三个高度保守的半胱氨酸桥中的两个，这些半胱氨酸桥通常存在于这些小的碱性蛋白模块中。在本研究中，通过多维核磁共振光谱法解析了Conk-S1的三维结构。重组Conk-S1的溶液结构表明，尽管缺少一个高度保守的二硫键交联，但仍存在库尼茨折叠。在Conk-S1中引入第三个同源二硫键会产生一种对Shaker钾通道具有相似亲和力的功能性毒素。Shaker通道孔内的孔突变可增强Conk-S1的亲和力，这表明Conk-S1与钾通道前庭存在相互作用。
