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

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• 作者：Ai-Hua Jin (1)
  Hemma Brandstaetter (1)
  Simon T Nevin (2)
  Chia Chia Tan (1)
  Richard J Clark (1)
  David J Adams (2)
  Paul F Alewood (1)
  David J Craik (1)
  Norelle L Daly (1)
  
• 刊名：BMC Structural Biology
• 出版年：2007
• 出版时间：December 2007
• 年：2007
• 卷：7
• 期：1
• 全文大小：1416KB
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• 作者单位：Ai-Hua Jin (1)
  Hemma Brandstaetter (1)
  Simon T Nevin (2)
  Chia Chia Tan (1)
  Richard J Clark (1)
  David J Adams (2)
  Paul F Alewood (1)
  David J Craik (1)
  Norelle L Daly (1)
  
  1. Institute for Molecular Bioscience, Australian Research Council Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane, QLD 4072, Australia
  2. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
  
• ISSN：1472-6807

文摘

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 α-conotoxins is variable, leading to the classification of sub-families. BuIA is the only α-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 α-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.