Signal transduction and gating mechanism

Signal transduction

In the strychnine and glycine bound states, the binding of these 2 molecules causes a conformational change in the β-sheets, leading to changes in the junction between the ECD and TMD. At the neurotransmitter binding site in the strychnine bound state, the displacement of Arg81 and Arg135 in the β-sheets and the opening of the C loop causes an expansion.  

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Figure 1-2 shows the strychnine bound state (cyan) and the glycine bound state (green). Figure 1 shows the arginines in purple for the strychnine-bound state and yellow for the glycine state. C loops in figure 2 show that of the strychnine state is in a more open conformation 

When glycine is bound, the changes in the ECD are passed onto the TMD via displacement of the β8–β9 loop
which is indirectly connected to the M2 helix. This loop is connected to the C loop so the changes shown
above cause the lower half of the helix to move towards the pore and the upper half to rotate outwards 

Figure 3 | The β8–β9 loop and M2 helix of the strychnine bound state is shown in brown while that of the glycine-bound state is shown in red. 

Comparing the glycine/ivermectin state to the glycine-bound state, the binding of ivermectin causes the
lower half of the M2 helix to move slightly towards the lumen of the pore. However the ECDs of the
2 states are more similar.

Figures 4-5 | The glycine/ivermectin bound state (pink) is overlaid on the glycine bound state (green) . Figure 5 shows the M2 helix in the glycine/ivermectin bound state (which is shown in blue) is tilted more towards the pore lumen compared to that of the glycine state in yellow.