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A 3D structural model of RsXXVIA, an ω-conotoxin

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Abstract

The pharmacological relevance of peptides isolated from cone snails is gaining interest, particularly for pain management. Conotoxins are small well-structured peptides with specific functions over a number of specific physiological targets. Despite the large number and variety of toxins that these organisms can produce, only a handful of three-dimensional structures has been experimentally determined. Theoretical models of toxins, developed with bioinformatics method, contribute to the understanding of the structure and function of these peptides. RsXXVIA is a conotoxin previously isolated from the Conus regularis venom that has been shown to block N-type calcium channels. In this work, we modeled 12 theoretical cysteine frameworks (disulfide bonds) to elucidate the 3D structure of RsXXIVA to explain its activity. We used, as a template, the ω-conotoxin MVIIA (ziconotide), a prototype conotoxin with high sequence similarity to RsXXVIA. Particularly, the spatial arrangement of two amino acid residues, Lys2 and Tyr13 (in ziconotide), responsible for the pharmacological activity was taken into account. Remarkably, 3D models rendered a particularly suitable spatial disposition of key amino acids responsible for the activity on the N-type calcium channel. Additionally, this work explains, through computational models, how the conotoxin might be acting on the channel, thus, paving the way to find the principal RsXXVIA’s physiological target.

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Acknowledgments

This work was possible thanks to the support of the Posgrado en Ciencias Biológicas de la Universidad Nacional Autónoma de México. This paper fulfills the requirement for the principal author to obtain the PhD degree in the Posgrado en Ciencias Biológicas de la UNAM. This work was supported by a grant from the Consejo Nacional de Ciencia y Tecnología (CONACyT-Mexico) with the number 189808.

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Correspondence to Roberto Arreguín-Espinosa.

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The authors declare that they have no conflict of interest.

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Román-González, S.A., Robles-Gómez, E.E., Reyes, J. et al. A 3D structural model of RsXXVIA, an ω-conotoxin. Struct Chem 28, 901–909 (2017). https://doi.org/10.1007/s11224-016-0877-8

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Keywords

  • Conotoxin
  • Ion channels
  • Cone snail
  • Peptide
  • Pharmacology