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Sci Rep
2020 May 05;101:7529. doi: 10.1038/s41598-020-64258-z.
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The mechanism of loop C-neonicotinoid interactions at insect nicotinic acetylcholine receptor α1 subunit predicts resistance emergence in pests.
Shimada S
,
Kamiya M
,
Shigetou S
,
Tomiyama K
,
Komori Y
,
Magara L
,
Ihara M
,
Matsuda K
.
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Neonicotinoids selectively modulate insect nicotinic acetylcholine receptors (insect nAChRs). Studies have shown that serine with ability to form a hydrogen bond in loop C of some insect nAChR α subunits and glutamate with a negative charge at the corresponding position in vertebrate nAChRs may contribute to enhancing and reducing the neonicotinoid actions, respectively. However, there is no clear evidence what loop C properties underpin the target site actions of neonicotinoids. Thus, we have investigated the effects of S221A and S221Q mutations in loop C of the Drosophila melanogaster Dα1 subunit on the agonist activity of imidacloprid and thiacloprid for Dα1/chicken β2 nAChRs expressed in Xenopus laevis oocytes. The S221A mutation hardly affected either the affinity or efficacy for ACh and imidacloprid, whereas it only slightly reduced the efficacy for thiacloprid on the nAChRs with a higher composition ratio of β2 to Dα1 subunits. The S221Q mutation markedly reduced the efficacy of the neonicotinoids for the nAChRs with a higher composition of the β2 subunit lacking basic residues critical for binding neonicotinoids. Hence, we predict the possibility of enhanced neonicotinoid resistance in pest insect species by a mutation of the serine when it occurs in the R81T resistant populations lacking the basic residue in loop D of the β1 subunit.
Figure 1. Imidacloprid and thiacloprid tested in this study, Figures are illustrated as ball and sticks where carbons, hydrogens, nitrogens, chlorine and sulfur are colored white, sky blue, blue, light green and yellow, respectively. Delocalized double bonds are shown as broken lines. Each chemical structure was drawn using Chem 3D combined with Chem Draw (PerkinElmer, Waltham, MA, USA).
Figure 2. Agonist actions of ACh on wild type, S221A mutant and S221Q mutant of (Dα1)3(β2)2 and (Dα1)2(β2)3 nAChRs expressed in X. laevis oocytes. Current responses to ACh for the nAChRs tested are shown above concentration-response data. Horizontal lines indicate bath applications of ACh. Each data plotted represents mean ± standard error of the mean (n = 5).
Figure 3. Agonist actions of imidacloprid and thiacloprid on wild type and S221A mutant Dα1β2 nAChRs expressed in X. laevis oocytes. In (A) and (B), inward current oocytes expressing the nAChRs in response to imidacloprid are shown above the concentration-response curves. Horizontal lines indicate bath applications of imidacloprid and thiacloprid. (a) Concentration-normalized response relationships of imidacloprid for the wild type and mutant (Dα1)3(β2)2 and (Dα1)2(β2)3 nAChRs. (b) Concentration-normalized response relationships of thiacloprid for the wild type and mutant (Dα1)3(β2)2 and (Dα1)2(β2)3 nAChRs. Each data plotted represents mean ± standard error of the mean (n = 5).
Figure 4. Agonist actions of imidacloprid and thiacloprid on wild type and S221Q mutant Dα1β2 nAChRs expressed in Xenopus laevis oocytes. Current responses to imidacloprid are shown above the concentration-response curves. Horizontal lines indicate bath applications of imidacloprid and thiacloprid. (a) Concentration-normalized response relationships of imidacloprid for the wild type and mutant (Dα1)3(β2)2 and (Dα1)2(β2)3 nAChRs. (b) Concentration-normalized response relationships of thiacloprid for the wild type and mutant (Dα1)3(β2)2 and (Dα1)2(β2)3 nAChRs. Each data plotted represents mean ± standard error of the mean (n = 5).
Figure 5. Models of Dα1/Dα1 subunit interface complexed with thiacloprid in (a) wild type and (b) S221A mutant (Dα1)3(β2)2 nAChRs. In the models, principal and complementary Dα1 subunits are illustrated as cartoon and colored pale cyan and yellow, respectively. Nitrogens, oxygen and sulfur atoms are colored blue, red and sand yellow, respectively, whereas carbons of thiacloprid are colored white. Electrostatic or hydrogen bond interactions are indicated by broken lines.
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