Tertiary Structure of Conotoxin GIIIA in Aqueous Solution

Jean Marc Lancelin, Daisuke Kohda, Shin ichi Tate, Fuyuhiko Inagaki, Yuchio Yanagawa, Teruo Abe, Mei Satake

Research output: Contribution to journalArticle

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Abstract

The three-dimensional structure of conotoxin GIIIA, an important constituent of the venom from the marine hunting snail Conus geographus L., was determined in aqueous solution by two-dimensional proton nuclear magnetic resonance and simulated annealing based methods. On the basis of 162 assigned nuclear Overhauser effect (NOE) connectivities obtained at the medium field strength frequency of 400 MHz, 74 final distance constraints of sequential and tertiary ones were derived and used together with 18 torsion angle (ϕ, χ1) constraints and 9 distance constraints derived from disulfide bridges. A total of 32 converged structures were obtained from 200 runs of calculations. The atomic root-mean-square (RMS) difference about the mean coordinate positions (excluding the terminal residues 1 and 22) is 0.8 Â for backbone atoms (N, Cα, C). Conotoxin GIIIA is characterized by a particular folding of the 22 amino acid peptidic chain, which is stabilized by three disulfide bridges arranged in cage at the center of a discoidal structure of approximately 20-Å diameter. The seven cationic side chains of lysine and arginine residues project radially into the solvent and form potential sites of interaction with the skeletal muscle sodium channel for which the toxin is a strong inhibitor. The present results provide a molecular basis to elucidate the remarkable physiological properties of this neurotoxin.

Original languageEnglish
Pages (from-to)6908-6916
Number of pages9
JournalBiochemistry
Volume30
Issue number28
DOIs
Publication statusPublished - Jul 1 1991

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Conotoxins
Disulfides
Nuclear magnetic resonance
Conus Snail
Sodium Channels
Venoms
Neurotoxins
Simulated annealing
Torsional stress
Lysine
Arginine
Muscle
Protons
Skeletal Muscle
Magnetic Resonance Spectroscopy
Amino Acids
Atoms

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Lancelin, J. M., Kohda, D., Tate, S. I., Inagaki, F., Yanagawa, Y., Abe, T., & Satake, M. (1991). Tertiary Structure of Conotoxin GIIIA in Aqueous Solution. Biochemistry, 30(28), 6908-6916. https://doi.org/10.1021/bi00242a014

Tertiary Structure of Conotoxin GIIIA in Aqueous Solution. / Lancelin, Jean Marc; Kohda, Daisuke; Tate, Shin ichi; Inagaki, Fuyuhiko; Yanagawa, Yuchio; Abe, Teruo; Satake, Mei.

In: Biochemistry, Vol. 30, No. 28, 01.07.1991, p. 6908-6916.

Research output: Contribution to journalArticle

Lancelin, JM, Kohda, D, Tate, SI, Inagaki, F, Yanagawa, Y, Abe, T & Satake, M 1991, 'Tertiary Structure of Conotoxin GIIIA in Aqueous Solution', Biochemistry, vol. 30, no. 28, pp. 6908-6916. https://doi.org/10.1021/bi00242a014
Lancelin JM, Kohda D, Tate SI, Inagaki F, Yanagawa Y, Abe T et al. Tertiary Structure of Conotoxin GIIIA in Aqueous Solution. Biochemistry. 1991 Jul 1;30(28):6908-6916. https://doi.org/10.1021/bi00242a014
Lancelin, Jean Marc ; Kohda, Daisuke ; Tate, Shin ichi ; Inagaki, Fuyuhiko ; Yanagawa, Yuchio ; Abe, Teruo ; Satake, Mei. / Tertiary Structure of Conotoxin GIIIA in Aqueous Solution. In: Biochemistry. 1991 ; Vol. 30, No. 28. pp. 6908-6916.
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