Combined roles of loops C and D in the interactions of a neonicotinoid insecticide imidacloprid with the α4β2 nicotinic acetylcholine receptor

Toshima, Kayoko; Kanaoka, Satoshi; Yamada, Atsushi; Tarumoto, Kiyoshi; Akamatsu, Miki; Sattelle, David B.; Matsuda, Kazuhiko

doi:10.1016/j.neuropharm.2008.08.022

Cited by 28 publications

(17 citation statements)

References 35 publications

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“…23) On the other hand, the T77R and T77R+E79V mutants did not significantly change the pEC 50 value of acetamiprid, whereas a significant change was observed in the I max value. Although the effect of the T77R+E79V double mutation on imidacloprid agonist activity has been previously reported, 18,24) the present study is the first to show its effect on acetamiprid activity. Although it remains unclear whether insecticidal activity is dependent on either the pEC 50 or I max value, differences in the RFs between nitro-and cyano-substituted neonicotinoids were likely due to the effect of the R81T mutation on agonist affinity.…”

Section: Discussionmentioning

confidence: 46%

Association between the R81T mutation in the nicotinic acetylcholine receptor β1 subunit of <i>Aphis gossypii</i> and the differential resistance to acetamiprid and imidacloprid

Hirata

Kiyota

Matsuura

et al. 2015

Journal of Pesticide Science

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The Aphis gossypii clone, Kushima, which was first discovered in Miyazaki Prefecture, Japan, exhibits significant resistance to neonicotinoid insecticides. We investigated the resistance mechanism involved by sequencing the nicotinic acetylcholine receptor (nAChR) gene, by electrophysiological analysis, and by insecticidal tests in the presence or absence of the oxidase inhibitor, piperonyl butoxide. The Kushima clone showed higher resistance to nitro-substituted neonicotinoids, such as imidacloprid, than to cyano-substituted neonicotinoids, such as acetamiprid. Sequencing of the nAChR subunit genes of a susceptible clone and the Kushima clone revealed an R81T mutation in loop D of the β1 subunit in the resistant clone. This mutation led to a significant shift in the pEC 50 value of imidacloprid for the Drosophila melanogaster Dα2-chicken β2 subunit, while it barely affected the concentration-response curves of acetylcholine and acetamiprid.

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Section: Discussionmentioning

confidence: 46%

Association between the R81T mutation in the nicotinic acetylcholine receptor β1 subunit of <i>Aphis gossypii</i> and the differential resistance to acetamiprid and imidacloprid

Hirata

Kiyota

Matsuura

et al. 2015

Journal of Pesticide Science

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“…Therefore, the loop D basic residue (glutamine in AChBPs) plays a role in capturing neonicotinoids to strengthen the stacking and CH-hydrogen bonds. Consistent with this, mutations of the corresponding loop D residues to basic residues were found to dramatically enhance the neonicotinoid sensitivity of the chicken ␣7 (Shimomura et al, 2002) and ␣4␤2 nAChRs (Shimomura et al, 2006;Toshima et al, 2009). The selectivity-determining role of this residue can also explain, at least in part, why ␣7 having a glutamine (Gln89) residue in loop D is more neonicotinoid-sensitive than ␣4␤2 .…”

Section: Nicotinic Receptor-neonicotinoid Interactionsmentioning

confidence: 79%

Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

Matsuda

Kanaoka²,

Akamatsu³

et al. 2009

Mol Pharmacol

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118

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The nicotinic acetylcholine receptors (nAChRs) are targets for human and veterinary medicines as well as insecticides. Subtypeselectivity among the diverse nAChR family members is important for medicines targeting particular disorders, and pest-insect selectivity is essential for the development of safer, environmentally acceptable insecticides. Neonicotinoid insecticides selectively targeting insect nAChRs have important applications in crop protection and animal health. Members of this class exhibit strikingly diverse actions on their nAChR targets. Here we review the chemistry and diverse actions of neonicotinoids on insect and mammalian nAChRs. Electrophysiological studies on native nAChRs and on wild-type and mutagenized recombinant nAChRs have shown that basic residues particular to loop D of insect nAChRs are likely to interact electrostatically with the nitro group of neonicotinoids. In 2008, the crystal structures were published showing neonicotinoids docking into the acetylcholine binding site of molluscan acetylcholine binding proteins with homology to the ligand binding domain (LBD) of nAChRs. The crystal structures showed that 1) glutamine in loop D, corresponding to the basic residues of insect nAChRs, hydrogen bonds with the NO 2 group of imidacloprid and 2) neonicotinoid-unique stacking and CHbonds at the LBD. A neonicotinoid-resistant strain obtained by laboratory-screening has been found to result from target site mutations, and possible reasons for this are also suggested by the crystal structures. The prospects of designing neonicotinoids that are safe not only for mammals but also for beneficial insects such as honey bees (Apis mellifera) are discussed in terms of interactions with non-␣ nAChR subunits.

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“…The important role of loop C derives from a large body of work using x-ray crystallography (11,(35)(36)(37), molecular dynamics simulation (38 -40), site-directed mutagenesis (41)(42)(43)(44), and electrophysiology (45,46). The data from these studies demonstrates that loop C is flexible in the non-liganded form (22,37) and adopts distinct conformations upon agonist or antagonist binding.…”

Section: Discussionmentioning

confidence: 99%

Crystal Structures of a Cysteine-modified Mutant in Loop D of Acetylcholine-binding Protein

Brams

Gay

Saez

et al. 2011

Journal of Biological Chemistry

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Cys-loop receptors (CLRs) 2 belong to a class of ligandgated ion channels that are involved in fast synaptic transmission in the central nervous system and the neuromuscular junction. This transmission can either be excitatory or inhibitory depending on the charge of ions that pass through the ion conduction pathway of the channel. Excitatory transmission is mediated by nicotinic acetylcholine receptors (nAChR) and 5-HT 3 serotonin receptors, which selectively pass cations. On the other hand, inhibitory transmission is mediated by glycine receptors (GlyR) and ␥-aminobutyric acid (GABA A and GABA C ) receptors, which selectively conduct anions. In both types of receptors, the ion conduction pathway lies along the central axis formed by five channel subunits, which can either be identical for homomeric CLRs or non-identical for heteromeric CLRs. Opening and closing of the ion conduction pathway is controlled by a gate that is allosterically coupled to the extracellular ligand-binding domain (for a recent review see Ref. 1).Detailed structural data are still lacking for an intact eukaryotic CLR, but structural information has been obtained from 4 Å resolution electron microscopic images of the Torpedo nAChR (2) and higher resolution x-ray crystal structures of AChBP, a molluscan homolog of the extracellular domain of nAChRs (3, 4), the monomeric ␣1 nAChR subunit (5), and two prokaryotic homologs ELIC (6) and GLIC (7,8), which presumably represent the closed and open state of a CLR. Despite their different pharmacological properties, these CLRs share a common architectural arrangement of aromatic residues in their ligand-binding site. The ligand-binding site for CLRs is found at the interface between two subunits and ligands interact with amino acids from both the principal face (containing loops A, B, and C) and complementary face (containing loops D, E, and F). We have focused our attention on an aromatic residue that lies on the complementary face of the binding pocket and is highly conserved among eukaryotic and prokaryotic CLRs.Recently, we found that the tryptophan residue at position 55 of the rat ␣7 nAChR (Trp-55) was the site where synthetic * This research was supported, in whole or in part, by the Intramural Research Program of the National Institutes of Health, NIEHS (to E. A. G., J. C. S., and J. L. Y.), by G.0257.08), and the Belgian Federal Science Policy Office, Interuniversity Attraction Poles program (P6/31) (to J. T.), EU FP7 2020288 NeuroCypres (to C. U., A. B. S., and R. C. vd. S.), and KULeuven Onderzoekstoelage OT/08/048 (to S. V. S. and C. U.). □ S The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1. The atomic coordinates and structure factors (codes 2XZ6 and 2XZ5)

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Combined roles of loops C and D in the interactions of a neonicotinoid insecticide imidacloprid with the α4β2 nicotinic acetylcholine receptor

Cited by 28 publications

References 35 publications

Association between the R81T mutation in the nicotinic acetylcholine receptor β1 subunit of <i>Aphis gossypii</i> and the differential resistance to acetamiprid and imidacloprid

Association between the R81T mutation in the nicotinic acetylcholine receptor β1 subunit of <i>Aphis gossypii</i> and the differential resistance to acetamiprid and imidacloprid

Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

Crystal Structures of a Cysteine-modified Mutant in Loop D of Acetylcholine-binding Protein

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