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

BMC Struct Biol. 2007 Apr 20:7:28. doi: 10.1186/1472-6807-7-28.


Background: Alpha-conotoxins have exciting therapeutic potential based on their high selectivity and affinity for nicotinic acetylcholine receptors. The spacing between the cysteine residues in alpha-conotoxins is variable, leading to the classification of sub-families. BuIA is the only alpha-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 alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conotoxins / chemistry*
  • Conotoxins / metabolism*
  • Disulfides / chemistry*
  • Disulfides / metabolism*
  • Electrophysiology
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Oocytes
  • Patch-Clamp Techniques
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / metabolism
  • Xenopus


  • Conotoxins
  • Disulfides
  • Protein Isoforms
  • Receptors, Nicotinic