8FE1

Alpha1/BetaB Heteromeric Glycine Receptor in 1 mM Glycine 20 uM Ivermectin State

8FE1 の概要

• エントリーDOI: 10.2210/pdb8fe1/pdb
• EMDBエントリー: 29019
• 分子名称: Glycine receptor subunit alphaZ1, Glycine receptor beta subunit 2, GLYCINE, ... (8 entities in total)
• 機能のキーワード: glycine, channel, ivermectin, pentameric, membrane protein
• 由来する生物種: Danio rerio (zebrafish); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 294802.40

構造登録者

Gibbs, E.,Chakrapani, S. (登録日: 2022-12-05, 公開日: 2023-03-22, 最終更新日: 2025-06-04)

主引用文献

Gibbs, E.,Klemm, E.,Seiferth, D.,Kumar, A.,Ilca, S.L.,Biggin, P.C.,Chakrapani, S.
Conformational transitions and allosteric modulation in a heteromeric glycine receptor.
Nat Commun, 14:1363-1363, 2023

PubMed Abstract: Glycine Receptors (GlyRs) provide inhibitory neuronal input in the spinal cord and brainstem, which is critical for muscle coordination and sensory perception. Synaptic GlyRs are a heteromeric assembly of α and β subunits. Here we present cryo-EM structures of full-length zebrafish α1βGlyR in the presence of an antagonist (strychnine), agonist (glycine), or agonist with a positive allosteric modulator (glycine/ivermectin). Each structure shows a distinct pore conformation with varying degrees of asymmetry. Molecular dynamic simulations found the structures were in a closed (strychnine) and desensitized states (glycine and glycine/ivermectin). Ivermectin binds at all five interfaces, but in a distinct binding pose at the β-α interface. Subunit-specific features were sufficient to solve structures without a fiduciary marker and to confirm the 4α:1β stoichiometry recently observed. We also report features of the extracellular and intracellular domains. Together, our results show distinct compositional and conformational properties of αβGlyR and provide a framework for further study of this physiologically important channel.

PubMed: 36914669
DOI: 10.1038/s41467-023-37106-7

実験手法

ELECTRON MICROSCOPY (3 Å)