Characterization of the subunit composition and structure of adult human glycine receptors

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 beta subunit that permits clustering at the synapse through its interaction with scaffolding proteins. Here, we show that alpha 2 and beta 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 A resolutions and show how 4:1 stoichiometry is consistent with the structural features of alpha 2 beta GlyR. Furthermore, we show that one single beta subunit in each GlyR gives rise to the characteristic electrophysiological properties of heteromeric GlyR, while more beta subunits render GlyR non-conductive. A single beta subunit ensures a univalent GlyR-scaffold linkage, which means the scaffold alone regulates the cluster properties.

Automated summary

The strychnine-sensitive pentameric glycine receptor plays a crucial role in fast inhibitory neurotransmission in the mammalian nervous system. The study found that a single beta subunit in each GlyR is responsible for the characteristic electrophysiological properties of heteromeric GlyR.