Cryo-EM structures of ryanodine receptors and diamide insecticides reveal the mechanisms of selectivity and resistance.

Ryanodine Receptor Calcium Release Channel / metabolism Cryoelectron Microscopy Insecticides / pharmacology Animals Insecticide Resistance / genetics Benzamides / pharmacology ortho-Aminobenzoates / pharmacology Diamide / pharmacology Mutation Sulfones / pharmacology Insect Proteins / genetics Models, Molecular Fluorocarbons Phthalimides

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
20 Oct 2024
Historique:
received: 07 02 2024
accepted: 14 10 2024
medline: 21 10 2024
pubmed: 21 10 2024
entrez: 20 10 2024
Statut: epublish

Résumé

The resistance of pests to common insecticides is a global issue that threatens food production worldwide. Diamide insecticides target insect ryanodine receptors (RyRs), causing uncontrolled calcium release from the sarcoplasmic and endoplasmic reticulum. Despite their high potency and species selectivity, several resistance mutations have emerged. Using a chimeric RyR (chiRyR) approach and cryo-electron microscopy (cryo-EM), we investigate how insect RyRs engage two different diamide insecticides from separate families: flubendiamide, a phthalic acid derivative, and tetraniliprole, an anthranilic compound. Both compounds target the same site in the transmembrane region of the RyR, albeit with different poses, and promote channel opening through coupling with the pore-forming domain. To explore the resistance mechanisms, we also solve two cryo-EM structures of chiRyR carrying the two most common resistance mutations, I4790M and G4946E, both alone and in complex with the diamide insecticide chlorantraniliprole. The resistance mutations perturb the local structure, directly reducing the binding affinity and altering the binding pose. Our findings elucidate the mode of action of different diamide insecticides, reveal the molecular mechanism of resistance mutations, and provide important clues for the development of novel pesticides that can bypass the resistance mutations.

Identifiants

DOI: 10.1038/s41467-024-53490-0 PMID: 39428398
pubmed: 39428398
doi: 10.1038/s41467-024-53490-0
pii: 10.1038/s41467-024-53490-0
doi:

Substances chimiques

Ryanodine Receptor Calcium Release Channel 0
Insecticides 0
flubendiamide GEV84ZI4K6
Benzamides 0
chlorantranilipole 622AK9DH9G
ortho-Aminobenzoates 0
Diamide 10465-78-8
Sulfones 0
Insect Proteins 0
Fluorocarbons 0
Phthalimides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9056

Subventions

Organisme : Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)
ID : 2022YFE0108400
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32372580
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32272576
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 23K24067

Informations de copyright

© 2024. The Author(s).

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Auteurs

Lianyun Lin (L)

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Frontiers Science Center for Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, China.

Changshi Wang (C)

Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
ORCID: 0000-0001-5206-9737

Wenlan Wang (W)

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Frontiers Science Center for Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, China.

Heng Jiang (H)

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Frontiers Science Center for Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, China.

Takashi Murayama (T)

Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
ORCID: 0000-0002-3845-2980

Takuya Kobayashi (T)

Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
ORCID: 0000-0003-3992-1889

Hadiatullah Hadiatullah (H)

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Frontiers Science Center for Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, China.

Yu Seby Chen (YS)

Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
ORCID: 0000-0002-0793-2391

Shunfan Wu (S)

College of Plant Protection, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing Agricultural University, Nanjing, Jiangsu, China.
ORCID: 0000-0003-0096-147X

Yiwen Wang (Y)

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Frontiers Science Center for Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
ORCID: 0000-0003-2069-6685

Henryk Korza (H)

Syngenta Jealott's Hill International Research Centre, Bracknell, Berkshire, UK.

Yucheng Gu (Y)

Syngenta Jealott's Hill International Research Centre, Bracknell, Berkshire, UK.
ORCID: 0000-0002-6400-6167

Yan Zhang (Y)

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Frontiers Science Center for Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, China.
ORCID: 0000-0003-2031-0631

Jiamu Du (J)

Institute of Plant and Food Science, Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.
ORCID: 0000-0002-1337-0786

Filip Van Petegem (F)

Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. filip.vanpetegem@gmail.com.
ORCID: 0000-0003-2728-8537

Zhiguang Yuchi (Z)

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Frontiers Science Center for Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, China. yuchi@tju.edu.cn.
Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, China. yuchi@tju.edu.cn.
Guangdong Laboratory for Lingnan Modern Agriculture (Shenzhen Branch), Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China. yuchi@tju.edu.cn.
ORCID: 0000-0003-2595-9106

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Canaux calciques › Canal de libération du calcium du récepteur à la ryanodine › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions toxiques › Pesticides › Insecticides › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Eucaryotes › Animaux › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux insecticides › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Benzoates › Benzamides › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Benzoates › Aminobenzoates › ortho-Aminobenzoates › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Composés chimiques organiques › Composés azoïques › Tétraméthyl-diazènedicarboxamide › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Sulfones › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines d'arthropode › Protéines d'insecte › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures halogénés › Hydrocarbures fluorés › Fluorocarbones › Cryo-EM structures of ryanodine receptors and...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Isoindoles › Phtalimides › Cryo-EM structures of ryanodine receptors and...