In the retina of the eye, the protein rhodopsin responds to dim light in the membrane of the rod photoreceptor cell. To date, rhodopsin is one of the best studied G-protein-coupled-receptors (GPCR). Rhodopsin is composed of a protein and a prosthetic group. The apoprotein is referred to as opsin. The prosthetic group is 11-cis retinal. The latter group is a light-absorbing pigment molecule that determines the color of rhodopsin and its responsiveness to light. Under illumination, the 11-cis retinal chromophore isomerizes to an all-trans geometry after photon absorption. This leads to the formation of the active, G-protein-binding metarhodopsin II state. Metarhodopsin decays when all-trans retinal is photolyzed and the protonated retinylidene Schiff base is hydrolyzed from its binding pocket; a ligand-free opsin is generated. In a low pH buffer, opsin is converted to its active G-protein-binding state, known as Ops*. Ops* is stabilized by an 11-mer oligopeptide from the guanine nucleotide-binding protein G_αt subunit, in what is referred to as the Ops*-complex (fig. 1). This product resulting from the loss of all-trans-retinal from the metarhodpsin II-G_αCT complex, is considered to give an explanation for signal transfer from the receptor to the G-protein binding site (1, 2).

Ops* has seven transmembrane helices connected by extracellular and cytoplasmic loops, and the cytoplasmic helix8. The hydrophobic residues in TM 5 and 6 in Ops* form a hydrophobic surface for the interaction with G_αCT. When Ops* is induced by G_αCT binding (fig. 2), the Ops*-G_αCT complex shows changes in its protein interactions. The Ops*-G_αCT complex has 326 residues in opsin, but 22 of these residues are not observed, and are believed to have high mobility. Opsin in its G-protein-interacting conformation is shown in figure 1, with the Ops*-G_αCT complex lying along the membrane. Each of the Ops*-G_αCT molecules is perpendicular to the intercellular and the extracellular surfaces. Ops*-G_αCT shows electron density for Lys 296 in the retinal attachment site, but electron density is not observed in the retinal attachment site of Ops*. This indicates that G_αCT binding stabilizes the Lys 296 in a potential network of weak interactions involving Lys 296 in TM7, Tyr 268 in TM6, and Ser 186 and Glu 181 in loop E2. In one case, G_αCT homologues cannot bind to Ops* if a mutation occurs in the TM7-H8 kink (fig. 3) (1).

A single receptor interacts with various G proteins and then triggers diverse signaling pathways (2). The structure of Ops*-G_αCT provides clues about how the signal for GDP-GTP exchange is transferred from the receptor to the G-protein. First, the G_αt C-terminal α5 helix is modified to bind in the Ops*-G_αCT complex. With the help of the α5 helix, GDP is released during the Ops* and G_αCT interaction. In this case, the α5 helix acts as a transmission rod, and forces G-protein to be fixed for holding the receptor (1). On the other hand, whether single G-protein activates signal diversification is still controversial (2).