A Novel Dimeric Conotoxin, FrXXA, from the Vermivorous Cone Snail Conus fergusoni, of the Eastern Pacific, Inhibits Nicotinic Acetylcholine Receptors

Toxins (Basel). 2022 Jul 26;14(8):510. doi: 10.3390/toxins14080510.

Abstract

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.

Keywords: Conus fergusoni; Conus snails; alpha d-conotoxin; dimeric-peptides; nAChR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conotoxins* / chemistry
  • Conus Snail* / chemistry
  • Mice
  • Nicotinic Antagonists / metabolism
  • Nicotinic Antagonists / pharmacology
  • Receptors, Nicotinic* / metabolism
  • Snails / metabolism

Substances

  • Conotoxins
  • Nicotinic Antagonists
  • Receptors, Nicotinic

Grants and funding

This research was funded by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica-Universidad Nacional Autónoma de México (PAPIIT-UNAM) to E.L-V. and M.B.A., grant number IG200220, and Consejo Nacional de Ciencia y Tecnología (CONACYT) to E.L-V., grant number 153915. X.C.R-R was supported by fellowship 666534, from CONACYT.