3JAE

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

Summary for 3JAE

• Entry DOI: 10.2210/pdb3jae/pdb
• Related: 3JAD 3JAF
• EMDB information: 6344 6345 6346
• Descriptor: Glycine receptor subunit alphaZ1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: cys loop receptor, alpha-1 glycine receptor, glycine, signaling protein
• Biological source: Danio rerio (zebra fish)
• Total number of polymer chains: 5
• Total formula weight: 198239.70

Authors

Du, J.,Lu, W.,Wu, S.P.,Cheng, Y.F.,Gouaux, E. (deposition date: 2015-06-08, release date: 2015-09-09, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.9 Å)