Toxin insights into nicotinic acetylcholine receptors

Dutertre, S. and Lewis, R. J. (2006) Toxin insights into nicotinic acetylcholine receptors. Biochemical Pharmacology, 75 6: 661-670. doi:10.1016/j.bcp.2006.03.027

Author Dutertre, S.
Lewis, R. J.
Title Toxin insights into nicotinic acetylcholine receptors
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1016/j.bcp.2006.03.027
Open Access Status Not Open Access
Volume 75
Issue 6
Start page 661
End page 670
Total pages 10
Editor S.J. Enna
Place of publication Amsterdam
Publisher Elsevier Science Ltd
Language eng
Subject C1
320504 Toxicology (incl. Clinical Toxicology)
780103 Chemical sciences
Abstract Venomous species have evolved cocktails of bioactive peptides to facilitate prey capture. Given their often exquisite potency and target selectivity, venom peptides provide unique biochemical tools for probing the function of membrane proteins at the molecular level. in the field of the nicotinic acetylcholine receptors (nAChRs), the subtype specific snake alpha-neurotoxins and cone snail alpha-conotoxins have been widely used to probe receptor structure and function in native tissues and recombinant systems. However, only recently has it been possible to generate an accurate molecular view of these nAChR-toxin interactions. Crystal structures of AChBP, a homologue of the nAChR ligand binding domain, have now been solved in complex with alpha-cobratoxin, alpha-conotoxin PnIA and alpha-conotoxin Iml. The orientation of all three toxins in the ACh binding site confirms many of the predictions obtained from mutagenesis and docking simulations on homology models of mammalian nAChR. The precise understanding of the molecular determinants of these complexes is expected to contribute to the development of more selective nAChR modulators. In this commentary, we review the structural data on nAChR-toxin interactions and discuss their implications for the design of novel ligands acting at the nAChR. (c) 2006 Elsevier Inc. All rights reserved.
Keyword nicotinic acetylcholine receptor (nAChR)
homology models
docking simulations
X-ray protein structure
structure-activity relationships (SAR)
Alpha-conotoxins Imi
Gated Ion Channels
Pairwise Interactions
Agonist Binding
Conus Peptides
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 19:25:22 EST