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Chimeric Investigations into the Diamide Binding Site on the Lepidopteran Ryanodine Receptor

Ewan Richardson, Bartek J. Troczka, Oliver Gutbrod, Ulrich Ebbinghaus-Kintscher, Martin S. Williamson, Christopher George Orcid Logo, Ralf Nauen, Thomas G. Emyr Davies

International Journal of Molecular Sciences, Volume: 22, Issue: 23, Start page: 13033

Swansea University Author: Christopher George Orcid Logo

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DOI (Published version): 10.3390/ijms222313033

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 wer...

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Published in: International Journal of Molecular Sciences
ISSN: 1422-0067
Published: MDPI AG 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa58894
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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.
Keywords: diamide insecticides, chlorantraniliprole, flubendiamide, lepidoptera, Plutella xylostella, binding site
College: Faculty of Medicine, Health and Life Sciences
Funders: Bayer CropScience through a Biotechnology and Biological Sciences Research Council-funded Industrial studentship (BBSRC grant NoBB/N504075/1); Biotechnology and Biological Sciences Research Council, UK.
Issue: 23
Start Page: 13033