3JAF

Structure of alpha-1 glycine receptor by single particle electron cryo-microscopy, glycine/ivermectin-bound state

3JAF の概要

• エントリーDOI: 10.2210/pdb3jaf/pdb
• 関連するPDBエントリー: 3JAD 3JAE
• EMDBエントリー: 6344 6345 6346
• 分子名称: Glycine receptor subunit alphaZ1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, (2aE,4E,5'S,6S,6'R,7S,8E,11R,13R,15S,17aR,20R,20aR,20bS)-6'-[(2S)-butan-2-yl]-20,20b-dihydroxy-5',6,8,19-tetramethyl-17 -oxo-3',4',5',6,6',10,11,14,15,17,17a,20,20a,20b-tetradecahydro-2H,7H-spiro[11,15-methanofuro[4,3,2-pq][2,6]benzodioxacy clooctadecine-13,2'-pyran]-7-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-alpha-L-arabino-hexopyranosyl)-3-O-methyl-alpha-L-arabino-hexopyranoside (3 entities in total)
• 機能のキーワード: cys loop receptor, alpha-1 glycine receptor, glycine, ivermectin, signaling protein
• 由来する生物種: Danio rerio (zebra fish)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 202615.16

構造登録者

Du, J.,Lu, W.,Wu, S.P.,Cheng, Y.F.,Gouaux, E. (登録日: 2015-06-08, 公開日: 2015-09-09, 最終更新日: 2024-10-16)

主引用文献

Du, J.,Lu, W.,Wu, S.,Cheng, Y.,Gouaux, E.
Glycine receptor mechanism elucidated by electron cryo-microscopy.
Nature, 526:224-229, 2015

PubMed Abstract: The strychnine-sensitive glycine receptor (GlyR) mediates inhibitory synaptic transmission in the spinal cord and brainstem and is linked to neurological disorders, including autism and hyperekplexia. Understanding of molecular mechanisms and pharmacology of glycine receptors has been hindered by a lack of high-resolution structures. Here we report electron cryo-microscopy structures of the zebrafish α1 GlyR with strychnine, glycine, or glycine and ivermectin (glycine/ivermectin). Strychnine arrests the receptor in an antagonist-bound closed ion channel state, glycine stabilizes the receptor in an agonist-bound open channel state, and the glycine/ivermectin complex adopts a potentially desensitized or partially open state. Relative to the glycine-bound state, strychnine expands the agonist-binding pocket via outward movement of the C loop, promotes rearrangement of the extracellular and transmembrane domain 'wrist' interface, and leads to rotation of the transmembrane domain towards the pore axis, occluding the ion conduction pathway. These structures illuminate the GlyR mechanism and define a rubric to interpret structures of Cys-loop receptors.

PubMed: 26344198
DOI: 10.1038/nature14853

実験手法

ELECTRON MICROSCOPY (3.8 Å)