Assembly of the β2-AR-Gs complex

A peptide of approximately 20 Amino acids generated from the C–terminus of Gs was fused to the C-terminus of the β2AR (figure 1). This caused a 27 fold increase in agonist affinity to the receptor. This shows that the peptide fusion to the C-terminus of the β2AR caused a functional interaction to occur within the receptor and could potentially be the first step of β2AR-Gs complex formation.

Figure 1: shows the addition of the C-terminal 20 amino 
acid peptide of the Gs protein to the C-terminus 
of the β2AR (Rasmussen et al, 2011)

In order to enable the intial interaction of the β2AR with the Gs protein, the C-terminus of the α5-helix must move away from the β6 strand in order to allow the agonist bound β2AR to interact with the GαsRas (see figure 2).

For further interactions between the β2AR and the N-terminus of the Gαs, the GαsRas must rotate relative to the receptor and this in turn will cause subsequent conformational changes in both the β2AR and the GαsRas (see figure 2).

Figure 2a. The initial position of GαsRas on the β2AR as observed in the β2AR-Gs complex

Figure 2b. The final position (yellow) of GαsRas on the β2AR as observed in the β2AR-Gs complex after a conformational change

Exactly when the GDP is released during the formation of the complex is currently unknown; however, it is thought that the GDP is released when GαsAH dissociates from the GαsRas. This may be a coincidental event or the energy generated from the release of GDP may enable this dissociation to take place.