8DN4

Cryo-EM structure of human Glycine Receptor alpha-1 beta heteromer, glycine-bound state3(desensitized state)

Summary for 8DN4

• Entry DOI: 10.2210/pdb8dn4/pdb
• EMDB information: 27554
• Descriptor: Glycine receptor subunit alpha-1, Glycine receptor subunit beta,Green fluorescent protein,Glycine receptor beta, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: glycine receptor subunit alpha-1, glycine receptor subunit beta, green fluorescent protein, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 248753.70

Authors

Liu, X.,Wang, W. (deposition date: 2022-07-10, release date: 2023-10-11, Last modification date: 2024-10-30)

Primary citation

Liu, X.,Wang, W.
Asymmetric gating of a human hetero-pentameric glycine receptor.
Nat Commun, 14:6377-6377, 2023

PubMed Abstract: Hetero-pentameric Cys-loop receptors constitute a major type of neurotransmitter receptors that enable signal transmission and processing in the nervous system. Despite intense investigations into their working mechanism and pharmaceutical potentials, how neurotransmitters activate these receptors remains unclear due to the lack of high-resolution structural information in the activated open state. Here we report near-atomic resolution structures resolved in digitonin consistent with all principle functional states of the human α1β GlyR, which is a major Cys-loop receptor that mediates inhibitory neurotransmission in the central nervous system of adults. Glycine binding induces cooperative and symmetric structural rearrangements in the neurotransmitter-binding extracellular domain but asymmetrical pore dilation in the transmembrane domain. Symmetric response in the extracellular domain is consistent with electrophysiological data showing cooperative glycine activation and contribution from both α1 and β subunits. A set of functionally essential but differentially charged amino acid residues in the transmembrane domain of the α1 and β subunits explains asymmetric activation. These findings provide a foundation for understanding how the gating of the Cys-loop receptor family members diverges to accommodate specific physiological environments.

PubMed: 37821459
DOI: 10.1038/s41467-023-42051-6

Experimental method

ELECTRON MICROSCOPY (4.1 Å)