7MLV

Cryo-EM reveals partially and fully assembled native glycine receptors,homomeric tetramer

7MLV の概要

• エントリーDOI: 10.2210/pdb7mlv/pdb
• EMDBエントリー: 23911
• 分子名称: 3D1 Fab Light Chain, 3D1 Fab Heavy Chain, Glycine receptor alpha 1, ... (9 entities in total)
• 機能のキーワード: glycine receptor, ion channel, homomeric tetramer, membrane protein, signaling protein
• 由来する生物種: Rattus norvegicus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 313561.21

構造登録者

Zhu, H.,Gouaux, E. (登録日: 2021-04-29, 公開日: 2021-09-29, 最終更新日: 2024-10-09)

主引用文献

Zhu, H.,Gouaux, E.
Architecture and assembly mechanism of native glycine receptors.
Nature, 599:513-517, 2021

PubMed Abstract: Glycine receptors (GlyRs) are pentameric, 'Cys-loop' receptors that form chloride-permeable channels and mediate fast inhibitory signalling throughout the central nervous system. In the spinal cord and brainstem, GlyRs regulate locomotion and cause movement disorders when mutated. However, the stoichiometry of native GlyRs and the mechanism by which they are assembled remain unclear, despite extensive investigation. Here we report cryo-electron microscopy structures of native GlyRs from pig spinal cord and brainstem, revealing structural insights into heteromeric receptors and their predominant subunit stoichiometry of 4α:1β. Within the heteromeric pentamer, the β(+)-α(-) interface adopts a structure that is distinct from the α(+)-α(-) and α(+)-β(-) interfaces. Furthermore, the β-subunit contains a unique phenylalanine residue that resides within the pore and disrupts the canonical picrotoxin site. These results explain why inclusion of the β-subunit breaks receptor symmetry and alters ion channel pharmacology. We also find incomplete receptor complexes and, by elucidating their structures, reveal the architectures of partially assembled α-trimers and α-tetramers.

PubMed: 34555840
DOI: 10.1038/s41586-021-04022-z

実験手法

ELECTRON MICROSCOPY (4.1 Å)