6. Activation and deactivation of Galpha

  1. Now, we will define how the ligated receptor induces a GDP->GTP exchange in the Galpha molecule while this is bound on one site by the receptor and on the other site by Gbetagamma. Load this complex species into the view by double-clicking it.

  2. Under 'Relations' click 'New' and then select 'Create/Edit Transformation'.

  3. On the 'Transformation' page, set the initial state of Galpha to GTP 'off' and the result state to GTP 'on'. Define a rate (3 per second) and (optionally) a name. Setting the annotation information about the stimulatory nature of this reaction will later on allow for more expressive visualization of the reaction network. Click 'Save'.

  4. Go back to the complex page.

    The file "G_protein_6.4.dbf" represents the model as it should be at this stage of the tutorial.

  5. Next, we will define how the activated (GTP state) Galpha returns to the GDP state so it can bind to Gbetagamma again and can be reused within a cycle of recruitments to the receptor, activation, deactivation etc..

    Load the Galpha complex species.

  6. Start creating a new transformation.

  7. We want to require that Galpha be unbound (to either the Receptor or Gbetagamma) to be able to undergo this transformation. Right-click (or on the Mac: control-Click) on the binding sites of Galpha and set them to unbound.

    The file "G_protein_6.7.dbf" represents the model as it should be at this stage of the tutorial.

    For the transformation, set the initial state of Galpha to GTP 'on' and the result state to GTP 'off'.

    Define a rate for this 'auto-GTPase' activity and (optionally) a name and annotation. We can set a descriptive name for the Galpha complexes involved (e.g. "Galpha_GTP_unbnd" and "Galpha_GDP_unbnd"). Then save and return to the complex page.