Isolation and characterization of alpha-conotoxin LsIA with potent activity at nicotinic acetylcholine receptors

Inserra, Marco C., Kompella, Shiva N., Vetter, Irina, Brust, Andreas, Daly, Norelle L., Cuny, Hartmut, Craik, David J., Alewood, Paul F., Adams, David J. and Lewis, Richard J. (2013) Isolation and characterization of alpha-conotoxin LsIA with potent activity at nicotinic acetylcholine receptors. Biochemical Pharmacology, 86 6: 791-799. doi:10.1016/j.bcp.2013.07.016


Author Inserra, Marco C.
Kompella, Shiva N.
Vetter, Irina
Brust, Andreas
Daly, Norelle L.
Cuny, Hartmut
Craik, David J.
Alewood, Paul F.
Adams, David J.
Lewis, Richard J.
Title Isolation and characterization of alpha-conotoxin LsIA with potent activity at nicotinic acetylcholine receptors
Formatted title
Isolation and characterization of α-conotoxin LsIA with potent activity at nicotinic acetylcholine receptors
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
1873-2968
Publication date 2013-09
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.bcp.2013.07.016
Volume 86
Issue 6
Start page 791
End page 799
Total pages 9
Place of publication Philadelphia, PA United States
Publisher Elsevier Inc.
Collection year 2014
Language eng
Formatted abstract
A new α-conotoxin LsIA was isolated from the crude venom of Conus limpusi using assay-guided RP-HPLC fractionation. Synthetic LsIA was a potent antagonist of α3β2, α3α5β2 and α7 nAChRs, with half-maximal inhibitory concentrations of 10,31 and 10 nM, respectively. The structure of LsIA determined by NMR spectroscopy comprised a characteristic disulfide bond-stabilized α-helical structure and disordered N-terminal region. Potency reductions of up to 9-fold were observed for N-terminally truncated analogues of LsIA at α7 and α3β2 nAChRs, whereas C-terminal carboxylation enhanced potency 3-fold at α3β2 nAChRs but reduced potency 3-fold at α7 nAChRs. This study gives further insight into α-conotoxin pharmacology and the molecular basis of nAChR selectivity, highlighting the influence of N-terminal residues and C-terminal amidation on conotoxin pharmacology.
Keyword Conus limpusi
Alpha Conotoxin
Nicotinic acetylcholine receptor
Electrophysiology
Nachr Subtype Selectivity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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