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Identification of Critical Elements Determining Toxins and Insecticide Affinity, Ligand Binding Domains and Channel Properties

  • Hélène Tricoire-Leignel
  • Steeve Hervé Thany
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 683)

Abstract

Insect nicotinic acetylcholine receptors have been objects of attention since the discovery of neonicotinoid insecticides. Mutagenesis studies have revealed that, although the detailed subunit composition of insect nicotinic acetylcholine receptors subtypes eludes us, the framework provided by mutagenesis analysis makes a picture of the subunits involved in the ligand binding and channel properties. In fact, many residues that line the channel or bind to the ligand seemed to be strongly conserved in particular in the N-terminal extracellular region and the second transmembrane domain which constitutes the ion-conducting pathway supporting the flux of ions as well as their discrimination. In fact, the positions are carried by loops B and C, respectively, which contain amino acids directly contributing to the acetylcholine binding site. Mutation of these residues accounts for insect resistance to neonicotinoid insecticides such as imidacloprid or a loss of specific binding. The discovery of the same mutation at homologous residues in different insect species or its conservation raises the intriguing question of whether a single mutation is essential to generate a resistance phenotype or whether some subunit confer insensitivity to ligand. Consequently, recent finding using information from Torpedo marmorata α1 subunit and soluble Aplysia californica and Lymnae stagnalis acetylcholine binding proteins from crystallization suggest that insect nAChR subunits had contributing amino acids in the agonist site structure which participate to affinity and pharmacological properties of these receptors. These new range of data greatly facilitate the understanding of toxin-nAChR interactions and the neonicotinoid binding and selectivity.

Keywords

Nicotinic Receptor Nicotinic Acetylcholine Receptor nAChR Subtype Neuronal Nicotinic Acetylcholine Receptor Neuronal Nicotinic Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  • Hélène Tricoire-Leignel
    • 1
  • Steeve Hervé Thany
    • 1
  1. 1.Laboratoire Récepteurs et Canaux Ioniques Membranaires (RCIM), UPRES EA 2647/USC INRA 2023, IFR 149 QUASAVUniversité d’Angers, UFR de SciencesAngersFrance

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