2ns3
From Proteopedia
Solution structure of ribbon BuIA
Structural highlights
FunctionCA1A_CONBU Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This peptide potently blocks numerous mammalian nAChR subtypes (alpha-6 or -3/beta-2 or -3 > alpha-6 or-3/beta-4 > alpha-3/beta-2 > alpha-3/beta-4 > alpha-4/beta-4 = alpha-2/beta-4 > alpha-7 > alpha-2/beta-2 >> alpha-4/beta-2). Recovery from toxin block is markedly slower for beta-4 versus beta-2 subunit-containing nAChRs. Thus, it represents a novel probe for distinguishing between beta-2 and beta-4-containing nAChRs. Publication Abstract from PubMedBACKGROUND: 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. Structure of alpha-conotoxin BuIA: influences of disulfide connectivity on structural dynamics.,Jin AH, Brandstaetter H, Nevin ST, Tan CC, Clark RJ, Adams DJ, Alewood PF, Craik DJ, Daly NL BMC Struct Biol. 2007 Apr 20;7:28. PMID:17445276[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
Categories: Conus bullatus | Large Structures | Adams DJ | Alewood PF | Brandstaetter H | Clark RJ | Craik DJ | Daly NL | Jin AH | Nevin ST | Tan CC