Structure of α-conotoxin BuIA: influences of disulfide connectivity on structural dynamics

Jin, Ai-Hua; Brandstaetter, Hemma; Nevin, Simon T.; Chia Chia Tan; Clark, Richard J.; Adams, David J.; Alewood, Paul F.; Craik, David J.; Daly, Norelle L.
January 2007
BMC Structural Biology;2007, Vol. 7, p28
Academic Journal
Background: α-Conotoxins have exciting therapeutic potential based on their high selectivity and affinity for nicotinic acetylcholine receptors. The spacing between the cysteine residues in a-conotoxins is variable, leading to the classification of sub-families. BuIA is the only a-conotoxin containing a 4/4 cysteine spacing and thus it is of significant interest to examine the structure of this conotoxin. Results: In the current study we show the native globular disulfide connectivity of BuIA displays multiple conformations in solution whereas the non-native ribbon isomer has a single well-defined conformation. Despite having multiple conformations in solution the globular form of BuIA displays activity at the nicotinic acetylcholine receptor, contrasting with the lack of activity of the structurally well-defined ribbon isomer. Conclusion: These findings are opposite to the general trends observed for a-conotoxins where the native isomers have well-defined structures and the ribbon isomers are generally disordered. This study thus highlights the influence of the disulfide connectivity of BuIA on the dynamics of the three-dimensional structure.


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