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TitleCharacterization of the subunit composition and structure of adult human glycine receptors.
Journal, issue, pagesNeuron, Vol. 109, Issue 17, Page 2707-22716.e6, Year 2021
Publish dateSep 1, 2021
AuthorsHailong Yu / Xiao-Chen Bai / Weiwei Wang /
PubMed AbstractThe strychnine-sensitive pentameric glycine receptor (GlyR) mediates fast inhibitory neurotransmission in the mammalian nervous system. Only heteromeric GlyRs mediate synaptic transmission, as they ...The strychnine-sensitive pentameric glycine receptor (GlyR) mediates fast inhibitory neurotransmission in the mammalian nervous system. Only heteromeric GlyRs mediate synaptic transmission, as they contain the β subunit that permits clustering at the synapse through its interaction with scaffolding proteins. Here, we show that α2 and β subunits assemble with an unexpected 4:1 stoichiometry to produce GlyR with native electrophysiological properties. We determined structures in multiple functional states at 3.6-3.8 Å resolutions and show how 4:1 stoichiometry is consistent with the structural features of α2β GlyR. Furthermore, we show that one single β subunit in each GlyR gives rise to the characteristic electrophysiological properties of heteromeric GlyR, while more β subunits render GlyR non-conductive. A single β subunit ensures a univalent GlyR-scaffold linkage, which means the scaffold alone regulates the cluster properties.
External linksNeuron / PubMed:34473954
MethodsEM (single particle)
Resolution3.6 - 3.8 Å
Structure data

23041

7kuy

EMDB-23041, PDB-7kuy:
Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, strychnine bound state
Method: EM (single particle) / Resolution: 3.6 Å

23148

7l31

EMDB-23148, PDB-7l31:
Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, strychnine bound state, 3.8 Angstrom
Method: EM (single particle) / Resolution: 3.8 Å

9403

5bkf

EMDB-9403, PDB-5bkf:
Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, Glycine bound, desensitized state
Method: EM (single particle) / Resolution: 3.6 Å

9404

5bkg

EMDB-9404, PDB-5bkg:
Cyro-EM structure of human Glycine Receptor alpha2-beta heteromer, glycine bound, (semi)open state
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-GLY:
GLYCINE

ChemComp-SY9:
STRYCHNINE / alkaloid*YM

Source
  • homo sapiens (human)
  • aequorea victoria (jellyfish)
KeywordsMEMBRANE PROTEIN / SIGNALING PROTEIN / glycine receptor / alpha2-beta hetero-pentamer / glycine / strychnine

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