title: Diversity of A-conotoxins of three worm-hunting cone snails (Conus brunneus, Conus nux, and Conus princeps) from the Mexican Pacific coast.
abstract: 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.
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Morales-González
authors.affiliation: 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.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Flores-Martínez
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zamora-Bustillos
authors.affiliation: Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico.
authors.forename: Reginaldo
authors.initials: R
authors.lastname: Rivera-Reyes
authors.affiliation: Departamento de Estudios para el Desarrollo Sustentable de Zonas Costeras, CUCSUR-Universidad de Guadalajara, Gómez Farías 82, San Patricio-Melaque, Jalisco 48980, Mexico.
authors.forename: Jesús Emilio
authors.initials: JE
authors.lastname: Michel-Morfín
authors.affiliation: Departamento de Estudios para el Desarrollo Sustentable de Zonas Costeras, CUCSUR-Universidad de Guadalajara, Gómez Farías 82, San Patricio-Melaque, Jalisco 48980, Mexico; Posgrado en Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Nayarit, Mexico.
authors.forename: Víctor
authors.initials: V
authors.lastname: Landa-Jaime
authors.affiliation: Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico.
authors.forename: Andrés
authors.initials: A
authors.lastname: Falcón
authors.affiliation: Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico. Electronic address: maguilar@unam.mx.
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Aguilar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry*; D052078:Conus Snail / Q000737:chemistry*; D008800:Mexico; D008969:Molecular Sequence Data; D010140:Pacific Ocean; D011498:Protein Precursors / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid
chemical_list: D020916:Conotoxins; D011498:Protein Precursors
keywords: A-conotoxin; Conotoxin precursor; Conus brunneus; Conus nux; Conus princeps; cDNA cloning