Allosteric Antagonist Model of aGPCR Activation.
A, in this model, the NTF behaves as an allosteric antagonist in two ways: (i) masking the stalk region and (ii) directly antagonizing the constitutive stalk-independent activity possessed by the 7TM region. B, conformational change of the NTF induced by ligand binding is sufficient to allow for enhanced stalk-dependent activity. C, ligand binding can also result in either NTF dissociation or a conformational change that relieves the inhibitory constraint of the NTF upon the 7TM region, such that both stalk-dependent and stalk-independent pathways are activated.