Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2707-2716.e6 |
Journal | Neuron |
Volume | 109 |
Issue number | 17 |
DOIs | |
State | Published - Sep 1 2021 |
Keywords
- cryo-EM structure
- heteromeric glycine receptor
- planar bilayer recording
- stepwise photobleaching
- stoichiometry
ASJC Scopus subject areas
- General Neuroscience