Toward a Model of the Receptor-G Protein Complex

Relatively few types of G proteins transduce the signals from a vast number of receptors. Each member of the heterotrimeric G protein family must, therefore, be capable of interacting with many different receptors. Additionally, many receptors are capable of activating multiple different G proteins. Although many interfacial contacts between these proteins have been described, the connections that define the coupling between receptors and specific G proteins remain unclear. 

Indeed, the observation that different agonists can affect which G proteins are activated by a given receptor supports a model where specific receptor conformations may be more or less favorable for coupling to specific G proteins (reviewed in Kenakin, 2003 Perez and Karnik, 2005). In one 

The most well-characterized receptor contact site in G proteins is the extreme C-terminus of Ga (Fig. 4). Structural information for this region is lacking as the C-terminus is either absent or disordered in most 

In addition to the C-terminus, several other regions of Ga have been implicated in receptor binding by a variety of experimental approaches (Fig. 4). Residues in the a4//16 loop contribute to the binding surface as demonstrated by alanine-scanning mutagenesis (Onrust et al, 1997), studies with chimeric Ga proteins (Bae et al., 1997, 1999), sequence analysis of conserved amino acids in Ga subclasses (Lichtarge et al., 1996), chemical cross-linking (Cai et al, 2001), and protection from tryptic proteolysis (Mazzoni and Hamm, 1996). The C-terminal 11 amino acids of Gat and 

Point-to-Point Interactions Between Receptors and G Proteins 

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