Fig. (2).

Schematic representation of a GPCR as a multi-domain protein, which is embedded into three micro-environments: the extra-cellular space (ECS), the plasma membrane (M) and the intra-cellular space (ICS). It is proposed that two regions (‘a’ and ‘b’) can be distinguished in a GPCR , namely a rather rigid core and a more plastic surrounding, respectively. The possible mechanisms for the RRI are also indicated. The chemico-physical features of the three environments as well as the action of allosteric modulators can affect both the conformation and/or the size of ‘a’ and ‘b’ regions and the mechanisms of RRI.