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Structure paper

TitleCryo-EM structures of ryanodine receptors and diamide insecticides reveal the mechanisms of selectivity and resistance.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 9056, Year 2024
Publish dateOct 20, 2024
AuthorsLianyun Lin / Changshi Wang / Wenlan Wang / Heng Jiang / Takashi Murayama / Takuya Kobayashi / Hadiatullah Hadiatullah / Yu Seby Chen / Shunfan Wu / Yiwen Wang / Henryk Korza / Yucheng Gu / Yan Zhang / Jiamu Du / Filip Van Petegem / Zhiguang Yuchi /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:39428398 / PubMed Central
MethodsEM (single particle)
Resolution3.28 - 3.91 Å
Structure data

EMDB-38398, PDB-8xji:
Structure of chimeric RyR complex with flubendiamide
Method: EM (single particle) / Resolution: 3.91 Å

EMDB-38417, PDB-8xkh:
Structure of chimeric RyR Complex with tetraniliprole
Method: EM (single particle) / Resolution: 3.87 Å

EMDB-38447, PDB-8xlf:
Structure of chimeric RyR
Method: EM (single particle) / Resolution: 3.62 Å

EMDB-38448, PDB-8xlh:
Structure of chimeric RyR-I4657M/G4819E
Method: EM (single particle) / Resolution: 3.62 Å

EMDB-38551: The map of chimeric RyR transmembrane domain in complex with flubendiamide after TMD local refinement
Method: EM (single particle) / Resolution: 3.82 Å

EMDB-38553: The map of chimeric RyR transmembrane domain in complex with tetraniliprole with TMD local refinement
Method: EM (single particle) / Resolution: 3.77 Å

EMDB-38908, PDB-8y40:
Structure of chimeric RyR-I4657M/G4819E complex with chlorantraniliprole
Method: EM (single particle) / Resolution: 3.58 Å

EMDB-60899: Structure of a chimeric RyR-I4657M/G4819E (local refinement of TMD)
Method: EM (single particle) / Resolution: 3.28 Å

EMDB-60900: Cryo-EM structure of ref-chiRyR (local refinement of TMD)
Method: EM (single particle) / Resolution: 3.68 Å

EMDB-60901: cryo-EM structure of chiRyR-I4657M/G4819E complex with CHL (local refinement of TMD)
Method: EM (single particle) / Resolution: 3.37 Å

Chemicals

PDB-1lvx:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-CFF:
CAFFEINE / medication*YM

PDB-1lv1:
Crystal Structure Analysis of the non-active site mutant of tethered HIV-1 protease to 2.1A resolution

ChemComp-F0U:
5-bromanyl-N-[4-chloranyl-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloranylpyridin-2-yl)pyrazole-3-carboxamide

Source
  • oryctolagus cuniculus (rabbit)
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Ryanodine receptor / Ion channel / tetraniliprole / chlorantraniliprole

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