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From Proteopedia
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Glycine Receptors (GlyRs) provide inhibitory neuronal input in the spinal cord and brainstem, which is critical for muscle coordination and sensory perception. Synaptic GlyRs are a heteromeric assembly of alpha and beta subunits. Here we present cryo-EM structures of full-length zebrafish alpha1beta(B)GlyR in the presence of an antagonist (strychnine), agonist (glycine), or agonist with a positive allosteric modulator (glycine/ivermectin). Each structure shows a distinct pore conformation with varying degrees of asymmetry. Molecular dynamic simulations found the structures were in a closed (strychnine) and desensitized states (glycine and glycine/ivermectin). Ivermectin binds at all five interfaces, but in a distinct binding pose at the beta-alpha interface. Subunit-specific features were sufficient to solve structures without a fiduciary marker and to confirm the 4alpha:1beta stoichiometry recently observed. We also report features of the extracellular and intracellular domains. Together, our results show distinct compositional and conformational properties of alpha(1)betaGlyR and provide a framework for further study of this physiologically important channel. | Glycine Receptors (GlyRs) provide inhibitory neuronal input in the spinal cord and brainstem, which is critical for muscle coordination and sensory perception. Synaptic GlyRs are a heteromeric assembly of alpha and beta subunits. Here we present cryo-EM structures of full-length zebrafish alpha1beta(B)GlyR in the presence of an antagonist (strychnine), agonist (glycine), or agonist with a positive allosteric modulator (glycine/ivermectin). Each structure shows a distinct pore conformation with varying degrees of asymmetry. Molecular dynamic simulations found the structures were in a closed (strychnine) and desensitized states (glycine and glycine/ivermectin). Ivermectin binds at all five interfaces, but in a distinct binding pose at the beta-alpha interface. Subunit-specific features were sufficient to solve structures without a fiduciary marker and to confirm the 4alpha:1beta stoichiometry recently observed. We also report features of the extracellular and intracellular domains. Together, our results show distinct compositional and conformational properties of alpha(1)betaGlyR and provide a framework for further study of this physiologically important channel. | ||
| - | + | , PMID:36914669<ref>PMID:36914669</ref> | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Alpha1/BetaB Heteromeric Glycine Receptor in 1 mM Glycine 20 uM Ivermectin State
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