Figure 5
Figure was drawn using Abobe Illustrator CC version 24.3 (https://www.adobe.com/kr/products/illustrator.html).
Schematic model of the activation mechanism of GlyRs for full and partial agonists. (a) The general activation mechanism of GlyRs includes at least three conformational states, whereby two conformations adopting a contracted ligand-bound ECD. Binding of a full agonist (red dot) induced an ECD closure of the resting receptor, while the ion channel is still shut (intermediate state). This ECD closure finally opens the ion channel and activates the receptor (open state). The ability of an agonist to change the conformation within the ECD (cEC50) was measured by MST, while the general ability to activate the receptor (aEC50) was determined by electrophysiological methods. (b) Binding of a partial agonist (purple) initiate an incomplete closure of the ECD (1). The receptor is either activated by a further ECD closure (2, grey) that leads to an ion channel opening (open state) or can directly open with a less contracted ECD (2, black). (c) GlyR activation in HEK293 cells and oocytes. Glycine binding to GlyRs in HEK293 cells is characterized by a contraction of the ECD and a rapid channel opening, reflected by similar cEC50 and aEC50 values. Binding of glycine to GlyRs in oocytes is also characterized by an efficient reorientation of the ECD with an impaired channel opening, possibly stabilizing an intermediate state with a contracted ECD and a closed channel pore.
