TITLE

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

AUTHOR(S)
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.
PUB. DATE
January 2007
SOURCE
BMC Structural Biology;2007, Vol. 7, p28
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
29323592

 

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics