![]() Their inhibitory input is essential for coordinated muscle movement, as manifested in hyperekplexia 3, a neurological disorder where mutations affecting GlyR clustering or function result in sporadic muscle movements. ![]() Glycine receptors (GlyRs) are chloride-conducting, pentameric ligand-gated ion channels (pLGIC) primarily found in spinal cord neurons where they mediate fast inhibitory neurotransmission 1, 2. Together, our results show distinct compositional and conformational properties of α 1βGlyR and provide a framework for further study of this physiologically important channel. We also report features of the extracellular and intracellular domains. Subunit-specific features were sufficient to solve structures without a fiduciary marker and to confirm the 4α:1β stoichiometry recently observed. Ivermectin binds at all five interfaces, but in a distinct binding pose at the β-α interface. Molecular dynamic simulations found the structures were in a closed (strychnine) and desensitized states (glycine and glycine/ivermectin). ![]() Each structure shows a distinct pore conformation with varying degrees of asymmetry. Here we present cryo-EM structures of full-length zebrafish α1β BGlyR in the presence of an antagonist (strychnine), agonist (glycine), or agonist with a positive allosteric modulator (glycine/ivermectin). Synaptic GlyRs are a heteromeric assembly of α and β subunits. Glycine Receptors (GlyRs) provide inhibitory neuronal input in the spinal cord and brainstem, which is critical for muscle coordination and sensory perception.
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