Chapter 5: Activation

After comparing the two structures, Hattori and Gouaux finally had enough empirical data to propose an activation mechanism:

1. ATP binding causes head and dorsal fin domains to clamp shut around the ATP.

2. The left flipper is pushed away from the binding site.

3. This causes the lower body domain to rotate about the rigid upper body domain expanding the extracellular vestibule and opening the lateral fenestrations.

4. This is transmitted to transmembrane domains 1 and 2 which expand like the iris of an eye, widening the pore for transport of cations entering via the lateral fenestrations.

Remember that this same set of movements must occur in all 3 subunits for complete ion channel activation. Therefore ion channel activation requires 3 ATPs.

To help you visualise these steps have a look at the image and video below:

In this animation, Hattori and Gouaux first show us the movements that occur in each subunit's extracellular domains when ATP binds. We then see the movements in the transmembrane domains. In the last part of the video all movements are put together to show complete trimer activation:

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