5Y9V

Crystal structure of diamondback moth ryanodine receptor N-terminal domain

Summary for 5Y9V

• Entry DOI: 10.2210/pdb5y9v/pdb
• Descriptor: Ryanodine receptor 1, GLYCEROL, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: diamondback moth, ryanodine receptor, ion channel, transport protein
• Biological source: Plutella xylostella (Diamondback moth)
• Total number of polymer chains: 2
• Total formula weight: 45351.89

Authors

Lin, L.,Yuchi, Z. (deposition date: 2017-08-28, release date: 2017-12-20, Last modification date: 2024-10-30)

Primary citation

Lin, L.,Liu, C.,Qin, J.,Wang, J.,Dong, S.,Chen, W.,He, W.,Gao, Q.,You, M.,Yuchi, Z.
Crystal structure of ryanodine receptor N-terminal domain from Plutella xylostella reveals two potential species-specific insecticide-targeting sites.
Insect Biochem. Mol. Biol., 92:73-83, 2017

PubMed Abstract: Ryanodine receptors (RyRs) are large calcium-release channels located in sarcoplasmic reticulum membrane. They play a central role in excitation-contraction coupling of muscle cells. Three commercialized insecticides targeting pest RyRs generate worldwide sales over 2 billion U.S. dollars annually, but the structure of insect RyRs remains elusive, hindering our understanding of the mode of action of RyR-targeting insecticides and the development of insecticide resistance in pests. Here we present the crystal structure of RyR N-terminal domain (NTD) (residue 1-205) at 2.84 Å resolution from the diamondback moth (DBM), Plutella xylostella, a destructive pest devouring cruciferous crops all over the world. Similar to its mammalian homolog, DBM RyR NTD consists of a beta-trefoil folding motif and a flanking alpha helix. Interestingly, two regions in NTD interacting with neighboring domains showed distinguished conformations in DBM relative to mammalian RyRs. Using homology modeling and molecular dynamics simulation, we created a structural model of the N-terminal three domains, showing two unique binding pockets that could be targeted by potential species-specific insecticides. Thermal melt experiment showed that the stability of DBM RyR NTD was higher than mammalian RyRs, probably due to a stable intra-domain disulfide bond observed in the crystal structure. Previously DBM NTD was shown to be one of the two critical regions to interact with insecticide flubendiamide, but isothermal titration calorimetry experiments negated DBM NTD alone as a major binding site for flubendiamide.

PubMed: 29191465
DOI: 10.1016/j.ibmb.2017.11.009

Experimental method

X-RAY DIFFRACTION (2.841 Å)