title: Structure of alpha-conotoxin BuIA: influences of disulfide connectivity on structural dynamics.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Institute for Molecular Bioscience, Australian Research Council Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane QLD, Australia. a.jin@imb.uq.edu.au <a.jin@imb.uq.edu.au>
authors: Ai-Hua
authors: AH
authors: Jin
authors: Hemma
authors: H
authors: Brandstaetter
authors: Simon T
authors: ST
authors: Nevin
authors: Chia Chia
authors: CC
authors: Tan
authors: Richard J
authors: RJ
authors: Clark
authors: David J
authors: DJ
authors: Adams
authors: Paul F
authors: PF
authors: Alewood
authors: David J
authors: DJ
authors: Craik
authors: Norelle L
authors: NL
authors: Daly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry* / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism*; D004594:Electrophysiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009865:Oocytes; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D014981:Xenopus
chemical_list: D020916:Conotoxins; D004220:Disulfides; D020033:Protein Isoforms; D011978:Receptors, Nicotinic