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Publication Abstract from PubMed

Ryanodine receptors (RyRs) are the molecular target of diamides, a new chemical class of insecticides. Diamide insecticides are used to control lepidopteran pests and were considered relatively safe for mammals and non-targeted beneficial insects, including honey bees. However, recent studies showed that exposure to diamides could cause long-lasting locomotor deficits of bees. Here we report the crystal structure of RyR N-terminal domain A (NTD-A) from the honeybee, Apis mellifera, at 2.5 A resolution. It shows a similar overall fold as the RyR NTD-A from mammals and the diamondback moth (DBM), Plutella xylostella, and still several loops located at the inter-domain interfaces show insect-specific or bee-specific structural features. A potential insecticide-binding pocket formed by loop9 and loop13 is conserved in lepidopteran but different in both mammals and bees, making it a good candidate targeting site for the development of pest-selective insecticides. Furthermore, a conserved intra-domain disulfide bond was observed in both DBM and bee RyR NTD-A crystal structures, which explains their higher thermal stability compared to mammalian RyR NTD-A. This work provides a basis for the development of novel insecticides with better selectivity between pests and bees by targeting a distinct site on pest RyRs, which would be a promising strategy to overcome the current toxicity problem.

Crystal structure of the N-terminal domain of ryanodine receptor from the honeybee, Apis mellifera.,Zhou Y, Wang W, Salauddin NM, Lin L, You M, You S, Yuchi Z Insect Biochem Mol Biol. 2020 Oct;125:103454. doi: 10.1016/j.ibmb.2020.103454., Epub 2020 Aug 8. PMID:32781205^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.