3jad

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

3jad, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Structural highlights 3jad is a 5 chain structure with sequence from Danio rerio. The November 2015 RCSB PDB Molecule of the Month feature on Glutamate-gated Chloride Receptors by David Goodsell is 10.2210/rcsb_pdb/mom_2015_11. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.9Å Ligands: Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLRA1_DANRE Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:10188956, PubMed:26344198). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol (By similarity).[UniProtKB:P23415] Publication Abstract from PubMed 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 alpha1 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. Glycine receptor mechanism elucidated by electron cryo-microscopy.,Du J, Lu W, Wu S, Cheng Y, Gouaux E Nature. 2015 Sep 7. doi: 10.1038/nature14853. PMID:26344198 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.