A Novel Dimeric Conotoxin, FrXXA, from the Vermivorous Cone Snail <i>Conus fergusoni</i>, of the Eastern Pacific, Inhibits Nicotinic Acetylcholine Receptors
Ximena C. Rodriguez-Ruiz,
Manuel B. Aguilar,
Mónica A. Ortíz-Arellano,
Helena Safavi-Hemami,
Estuardo López-Vera
Affiliations
Ximena C. Rodriguez-Ruiz
Posgrado en Ciencias del Mar y Limnología, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
Manuel B. Aguilar
Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico
Mónica A. Ortíz-Arellano
Laboratorio de Malacología, Facultad de Ciencias del Mar, Universidad Autónoma de Sinaloa, Mazatlán 82000, Mexico
Helena Safavi-Hemami
Department of Biomedical Science, University of Copenhagen, 1172 Copenhagen, Denmark
Estuardo López-Vera
Laboratorio de Toxinología Marina, Unidad Académica de Ecología y Biodiversidad Acuática, Instituto de Ciencias del Mar y Limnología, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
We isolated a new dimeric conotoxin with inhibitory activity against neuronal nicotinic acetylcholine receptors. Edman degradation and transcriptomic studies indicate a homodimeric conotoxin composed by two chains of 47 amino acid in length. It has the cysteine framework XX and 10 disulfide bonds. According to conotoxin nomenclature, it has been named as αD-FrXXA. The αD-FrXXA conotoxin inhibited the ACh-induced response on nAChR with a IC50 of 125 nM on hα7, 282 nM on hα3β2, 607 nM on α4β2, 351 nM on mouse adult muscle, and 447 nM on mouse fetal muscle. This is first toxin characterized from C. fergusoni and, at the same time, the second αD-conotoxin characterized from a species of the Eastern Pacific.
