Abstract
Alterations to amino acid residues G4946 and I4790, associated with resistance to diamide insecticides, suggests a location of diamide interaction within the pVSD voltage sensor-like domain of the insect ryanodine receptor (RyR). To further delineate the interaction site(s), targeted alterations were made within the same pVSD region on the diamondback moth (Plutella xylostella) RyR channel. The editing of five amino acid positions to match those found in the diamide insensitive skeletal RyR1 of humans (hRyR1) in order to generate a human–Plutella chimeric construct showed that these alterations strongly reduce diamide efficacy when introduced in combination but cause only minor reductions when introduced individually. It is concluded that the sites of diamide interaction on insect RyRs lie proximal to the voltage sensor-like domain of the RyR and that the main site of interaction is at residues K4700, Y4701, I4790 and S4919 in the S1 to S4 transmembrane domains.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Candidate diamide interacting residues on the insect ryanodine receptor (RyR) channel identified in previous studies were further scrutinized and assessed through alignment of 44 arthropod, nematode and vertebrate RyR amino acid sequences
Almost all the diamide resistance-associated mutations discovered to date (e.g., G4946E/V, I4790M/K, Y4701C/D) are concentrated within a 250 aa region close to the C-terminus of the protein, which in the 3D structure is located within the TM S1–S4 domain, peripheral to the channel pore (Figure 1b,c)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Diamides are a relatively new class of synthetic insecticidal compounds which act on the nerve–muscle boundary, causing contraction and paralysis of insect muscle cells. Members of the class vary in their spectrum of control, but the majority of these insecticides display extremely clean toxicological profiles. Diamide insecticides target the insect’s ryanodine receptor (RyR) and are highly effective against a variety of insect pests (especially those in the order Lepidoptera) but have little effect against mammalian RyRs
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