7M6N

Full length alpha1 Glycine receptor in presence of 0.1mM Glycine

7M6N の概要

• エントリーDOI: 10.2210/pdb7m6n/pdb
• EMDBエントリー: 23701
• 分子名称: Glycine receptor subunit alphaZ1, GLYCINE, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: ions ligands receptors, glycine receptor recombinant proteins, membrane protein
• 由来する生物種: Danio rerio (zebrafish)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 255589.93

構造登録者

Kumar, A.,Chakrapani, S. (登録日: 2021-03-26, 公開日: 2022-08-03, 最終更新日: 2024-10-16)

主引用文献

Kumar, A.,Kindig, K.,Rao, S.,Zaki, A.M.,Basak, S.,Sansom, M.S.P.,Biggin, P.C.,Chakrapani, S.
Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs.
Nat Commun, 13:4862-4862, 2022

PubMed Abstract: Nociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain and in the treatment of several neurological disorders. High-resolution mechanistic details of GlyR function and its modulation are just emerging. While it has been known that cannabinoids such as Δ-tetrahydrocannabinol (THC), the principal psychoactive constituent in marijuana, potentiate GlyR in the therapeutically relevant concentration range, the molecular mechanism underlying this effect is still not understood. Here, we present Cryo-EM structures of full-length GlyR reconstituted into lipid nanodisc in complex with THC under varying concentrations of glycine. The GlyR-THC complexes are captured in multiple conformational states that reveal the basis for THC-mediated potentiation, manifested as different extents of opening at the level of the channel pore. Taken together, these structural findings, combined with molecular dynamics simulations and functional analysis, provide insights into the potential THC binding site and the allosteric coupling to the channel pore.

PubMed: 35982060
DOI: 10.1038/s41467-022-32594-5

実験手法

ELECTRON MICROSCOPY (2.61 Å)