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-Structure paper
タイトル | Conformational transitions and allosteric modulation in a heteromeric glycine receptor. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 1363, Year 2023 |
掲載日 | 2023年3月13日 |
著者 | Eric Gibbs / Emily Klemm / David Seiferth / Arvind Kumar / Serban L Ilca / Philip C Biggin / Sudha Chakrapani / |
PubMed 要旨 | 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 ...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 α and β subunits. Here we present cryo-EM structures of full-length zebrafish α1βGlyR 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 β-α interface. Subunit-specific features were sufficient to solve structures without a fiduciary marker and to confirm the 4α:1β stoichiometry recently observed. We also report features of the extracellular and intracellular domains. Together, our results show distinct compositional and conformational properties of αβGlyR and provide a framework for further study of this physiologically important channel. |
リンク | Nat Commun / PubMed:36914669 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.0 Å |
構造データ | EMDB-29019, PDB-8fe1: |
化合物 | ChemComp-GLY: ChemComp-NAG: ChemComp-IVM: ChemComp-PX4: ChemComp-PLM: ChemComp-D10: |
由来 |
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キーワード | MEMBRANE PROTEIN / Glycine / Channel / Ivermectin / Pentameric |