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

Abstract

SUMMARYThe strychnine-sensitive pentameric Glycine Receptor (GlyR) mediates fast inhibitory neurotransmission in the mammalian nervous system. Only heteromeric GlyRs mediate synaptic transmission, since 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 α2β GlyR assembly mechanism. 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 renders GlyR non-conductive. A single β subunit ensures a univalent GlyR-scaffold linkage, which means the scaffold alone regulates the cluster properties.