Original paper

New binding sites of nicotinic acetylcholine receptors from Myzus persicae

Zhou, Yuxin; Han, Qing; Feng, Kun; Wang, Jingyi; Zhou, Haifeng; Wen, Ming; Duan, Hongxia; Wang, Yinliang; Ren, Bingzhong

Entomologia Generalis Volume 43 Number 2 (2023), p. 461 - 470

published: May 25, 2023
published online: Mar 22, 2023
manuscript accepted: Jan 20, 2023
manuscript revision received: Sep 12, 2022
manuscript revision requested: Jul 16, 2022
manuscript received: Apr 14, 2022

DOI: 10.1127/entomologia/2023/1662

BibTeX file

ArtNo. ESP146004302019, Price: 29.00 €

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Abstract

The green peach aphid, Myzus persicae, is the most serious agricultural pest worldwide, and its control relies mainly on insecticides such as neonicotinoids, due to their broad spectrum. Nicotinic acetylcholine receptors (nAChRs) are the target genes of neonicotinoids, and better knowledge of their toxicological mechanisms is crucial for developing new specific neonicotinoids, especially for non-model insects. In this study, we successfully cloned four nAChR α subunits in M. persicae and coexpressed them with Rattus norvegicus β2 in the Xenopus oocyte system. Screening results showed that Mpα1 and Mpα8 were narrowly tuned to sulfoxaflor and thiamethoxam, with EC50 values of 1.117 × 10−4 M and 9.681 × 10−5 M, respectively. Molecular modeling and docking results showed that a combination of positive (Lys) and aromatic (Trp) residues or positive (Lys) and polar (Ser) residues located at the interface of the corresponding α and β subunits of nAChR in Mpα1/ratβ2 or Mpα8/ratβ2 was the main contributor to ligand binding. Therefore, three residues (W143A, K144A and F260A) of Mpα1 and four residues (K63A, K134A, S146A and V290A) of Mpα8 were mutated to validate their contributions to the binding affinity of the corresponding ligand. In Mpα1, W143A resulted in a significantly lower sensitivity to sulfoxaflor than the other three mutations, and in Mpα8, S146A significantly reduced the response to thiamethoxam, suggesting crucial roles of these predicted hydrogen bonding sites in channel activation. These results provide evidence of the neonicotinoid toxicological mechanism in M. persicae and reveal new gene targets and binding sites for future pesticide design.

Keywords

Neonicotinoid • nAChR modeling • insecticide • sulfoxaflor • thiamethoxam •
Xenopus oocyte • aphid