The three-dimensional structure of the analgesic α-conotoxin, RgIA

Clark, Richard J.; Daly, Norelle L.; Halai, Reena; Nevin, Simon T.; Adams, David J.; Craik, David J.

doi:10.1016/j.febslet.2008.01.027

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Volume 582, Issue 5 , Pages 597-602, 5 March 2008

The three-dimensional structure of the analgesic α-conotoxin, RgIA

Edited by Christian Griesinger

Richard J. Clark
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia
Norelle L. Daly
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia
Reena Halai
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia
Simon T. Nevin
- School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia
David J. Adams
- School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia
David J. Craik
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia
- Corresponding author. Fax: +61 7 3346 2029.

Received 10 January 2008; accepted 17 January 2008. published online 31 January 2008.

Abstract

The α-conotoxin RgIA is a selective antagonist of the α9α10 nicotinic acetylcholine receptor and has been shown to be a potent analgesic and reduces nerve injury associated inflammation. RgIA was chemically synthesized and found to fold into two disulfide isomers, globular and ribbon. The native globular isomer inhibited ACh-evoked currents reversibly in oocytes expressing rat α9α10 nAChRs but the ribbon isomer was inactive. We determined the three-dimensional structure of RgIA using NMR methods to assist in elucidating the molecular role of RgIA in analgesia and inflammation.

Keywords: Conotoxin, Nuclear magnetic resonance, Analgesic, Oxidative folding, Disulfide isomers