8FE1

Alpha1/BetaB Heteromeric Glycine Receptor in 1 mM Glycine 20 uM Ivermectin State

Summary for 8FE1

• Entry DOI: 10.2210/pdb8fe1/pdb
• EMDB information: 29019
• Descriptor: Glycine receptor subunit alphaZ1, Glycine receptor beta subunit 2, GLYCINE, ... (8 entities in total)
• Functional Keywords: glycine, channel, ivermectin, pentameric, membrane protein
• Biological source: Danio rerio (zebrafish); More
• Total number of polymer chains: 5
• Total formula weight: 294802.40

Authors

Gibbs, E.,Chakrapani, S. (deposition date: 2022-12-05, release date: 2023-03-22, Last modification date: 2025-06-04)

Primary citation

Gibbs, E.,Klemm, E.,Seiferth, D.,Kumar, A.,Ilca, S.L.,Biggin, P.C.,Chakrapani, S.
Conformational transitions and allosteric modulation in a heteromeric glycine receptor.
Nat Commun, 14:1363-1363, 2023

PubMed Abstract: 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.

PubMed: 36914669
DOI: 10.1038/s41467-023-37106-7

Experimental method

ELECTRON MICROSCOPY (3 Å)