6M2W

Structure of RyR1 (Ca2+/Caffeine/ATP/CaM1234/CHL)

This is a non-PDB format compatible entry.

Summary for 6M2W

• Entry DOI: 10.2210/pdb6m2w/pdb
• EMDB information: 30067
• Descriptor: Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1, Peptidyl-prolyl cis-trans isomerase FKBP1B, Calmodulin-1, ... (8 entities in total)
• Functional Keywords: rabbit, ryanodine receptor1, chl., membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 2277714.85

Authors

Ma, R.,Haji-Ghassemi, O.,Ma, D.,Lin, L.,Samurkas, A.,Van Petegem, F.,Yuchi, Z. (deposition date: 2020-03-01, release date: 2020-09-02, Last modification date: 2024-03-27)

Primary citation

Ma, R.,Haji-Ghassemi, O.,Ma, D.,Jiang, H.,Lin, L.,Yao, L.,Samurkas, A.,Li, Y.,Wang, Y.,Cao, P.,Wu, S.,Zhang, Y.,Murayama, T.,Moussian, B.,Van Petegem, F.,Yuchi, Z.
Structural basis for diamide modulation of ryanodine receptor.
Nat.Chem.Biol., 16:1246-1254, 2020

PubMed Abstract: The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the highest-resolution cryo-electron microscopy (cryo-EM) structure of RyR1 in the open state, in complex with the anthranilic diamide chlorantraniliprole (CHL). The 3.2-Å local resolution map facilitates unambiguous assignment of the CHL binding site. The molecule induces a conformational change by affecting the S4-S5 linker, triggering channel opening. The binding site is further corroborated by mutagenesis data, which reveal how diamide insecticides are selective to the Lepidoptera group of insects over honeybee or mammalian RyRs. Our data reveal that several pests have developed resistance via two mechanisms, steric hindrance and loss of contact. Our results provide a foundation for the development of highly selective pesticides aimed at overcoming resistance and therapeutic molecules to treat human myopathies.

PubMed: 32807966
DOI: 10.1038/s41589-020-0627-5

Experimental method

ELECTRON MICROSCOPY (3.8 Å)