A new level of conotoxin diversity, a non-native disulfide bond connectivity in α-conotoxin AuIB reduces structural definition but increases biological activity

Authors

Julie L. Dutton, University of Queensland
Paramjit S. Bansal, University of Queensland
Ron C. Hogg, Centre Medical Universitaire
David J. Adams, University of QueenslandFollow
Paul F. Alewood, University of Queensland
David J. Craik, University of Queensland

RIS ID

106077

Publication Details

Dutton, J. L., Bansal, P. S., Hogg, R. C., Adams, D. J., Alewood, P. F. & Craik, D. J. (2002). A new level of conotoxin diversity, a non-native disulfide bond connectivity in α-conotoxin AuIB reduces structural definition but increases biological activity. Journal of Biological Chemistry, 277 (50), 48849-48857.

Abstract

α-Conotoxin AuIB and a disulfide bond variant of AuIB have been synthesized to determine the role of disulfide bond connectivity on structure and activity. Both of these peptides contain the 15 amino acid sequence GCCSYPPCFATNPDC, with the globular (native) isomer having the disulfide connectivity Cys(2-8 and 3-15) and the ribbon isomer having the disulfide connectivity Cys(2-15 and 3-8). The solution structures of the peptides were determined by NMR spectroscopy, and their ability to block the nicotinic acetylcholine receptors on dissociated neurons of the rat parasympathetic ganglia was examined. The ribbon disulfide isomer, although having a less well defined structure, is surprisingly found to have approximately 10 times greater potency than the native peptide. To our knowledge this is the first demonstration of a non-native disulfide bond isomer of a conotoxin exhibiting greater biological activity than the native isomer.