Figure 8.
Data-guided computational modeling of signal transduction from GPCRs to the cell interior in multi-Gγ systems. A, the reactions representing the proposed mechanism of GPCR-G protein activation used in the model. B, Gβγ fluctuation between active–inactive conformations (GβγPMn* ⇆ GβγPMn), which is assumed in the optimized model. C–E, concentrations of signaling entities (Gα(GDP)βγ, Gα(GDP), Gα(GTP), GβγPM, GβγPM*, GβγIM, and GβγEF) as a function of time for the four cases considered in the model (mono-HiAf-Gγ3, mono-MoAf-Gγ4, mono-LoAf-Gγ9, and equal mix of Gγ3, Gγ4 and Gγ9). F, Gβγ effector responses in a multi-Gγ system. The model predicts the responses are primarily dominated by the HiAf-Gγ. This indicates that the highest affinity Gγ of the pool dictates the signaling activity in general.