Morales-González Daniel, Flores-Martínez Ernesto, Zamora-Bustillos Roberto, Rivera-Reyes Reginaldo, Michel-Morfín Jesús Emilio, Landa-Jaime Víctor, Falcón Andrés, Aguilar Manuel B
Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico; Maestría en Ciencias (Neurobiología), Universidad Nacional Autónoma de México, Mexico.
Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico; Laboratorio de Genética Molecular, Instituto Tecnológico de Conkal, Conkal, Yucatán 97345, Mexico.
Peptides. 2015 Jun;68:25-32. doi: 10.1016/j.peptides.2015.02.002. Epub 2015 Feb 19.
Conus marine snails (∼500 species) are tropical predators that use venoms mainly to capture prey and defend themselves from predators. The principal components of these venoms are peptides that are known as "conotoxins" and generally comprise 7-40 amino acid residues, including 0-5 disulfide bridges and distinct posttranslational modifications. The most common molecular targets of conotoxins are voltage- and ligand-gated ion channels, G protein-coupled receptors, and neurotransmitter transporters, to which they bind, typically, with high affinity and specificity. Due to these properties, several conotoxins have become molecular probes, medicines, and leads for drug design. Conotoxins have been classified into genetic superfamilies based on the signal sequence of their precursors, and into pharmacological families according to their molecular targets. The objective of this work was to identify and analyze partial cDNAs encoding conotoxin precursors belonging to the A superfamily from Conus brunneus, Conus nux, and Conus princeps. These are vermivorous species of the Mexican Pacific coast from which only one A-conotoxin, and few O- and I2-conotoxins have been reported. Employing RT-PCR, we identified 30 distinct precursors that contain 13 different predicted mature toxins. With the exception of two groups of four highly similar peptides, these toxins are diverse at both the sequence and the physicochemical levels, and they belong to the 4/3, 4/4, 4/5, 4/6, and 4/7 structural subfamilies. These toxins are predicted to target diverse nicotinic acetylcholine receptor (nAChR) subtypes: nx1d, muscle; pi1a-pi1d, α3β2, α7, and/or α9α10; br1a, muscle, α3β4, and/or α4β2; and nx1a-nx1c/pi1g and pi1h, α3β2, α3β4, α9β10, and/or α7.
芋螺（约500种）是热带食肉动物，其毒液主要用于捕食猎物和抵御天敌。这些毒液的主要成分是被称为“芋螺毒素”的肽，通常由7至40个氨基酸残基组成，包括0至5个二硫键以及独特的翻译后修饰。芋螺毒素最常见的分子靶点是电压门控和配体门控离子通道、G蛋白偶联受体以及神经递质转运体，它们通常以高亲和力和特异性与之结合。由于这些特性，几种芋螺毒素已成为分子探针、药物以及药物设计的先导化合物。芋螺毒素已根据其前体的信号序列被分类为基因超家族，并根据其分子靶点被分类为药理学家族。这项工作的目的是鉴定和分析编码来自褐芋螺、核芋螺和王子芋螺的A超家族芋螺毒素前体的部分cDNA。这些是墨西哥太平洋沿岸的食虫物种，据报道从中仅发现了一种A-芋螺毒素以及少数O-和I2-芋螺毒素。通过逆转录聚合酶链反应（RT-PCR），我们鉴定出30种不同的前体，其中包含13种不同的预测成熟毒素。除了两组四个高度相似的肽外，这些毒素在序列和物理化学水平上均具有多样性，并且它们属于4/3、4/4、4/5、4/6和4/7结构亚家族。预计这些毒素靶向多种烟碱型乙酰胆碱受体（nAChR）亚型：nx1d，肌肉型；pi1a-pi1d，α3β2、α7和/或α9α10；br1a，肌肉型、α3β4和/或α4β2；以及nx1a-nx1c/pi1g和pi1h，α3β2、α3β4、α9β10和/或α7。
