Retinal ligand

FIGURE 2.1 A side view of the structure of the prototype G-protein-coupled, 7TM receptor rhodopsin. The x-ray structure of bovine rhodopsin is shown with horizontal gray lines, indicating the limits of the cellular lipid membrane. The retinal ligand is shown in a space-filling model as the cloud in the middle of the structure. The seven transmembrane (7TM) helices are shown in solid ribbon form. Note that TM-III is rather tilted (see TM-III at the extracellular and intracellular end of the helix) and that kinks are present in several of the other helices, such as TM-V (to the left), TM-VI (in front of the retinal), and TM-VII. In all of these cases, these kinks are due to the presence of a well-conserved proline residue, which creates a weak point in the helical structure. These kinks are believed to be of functional importance in the activation mechanism for 7TM receptors in general. Also note the amphipathic helix-VIII which is located parallel to the membrane at the membrane interface. 

Figure 3 Time series for the torsion connecting the ionone ring to the chain of rhodopsin s retinal ligand. All three panels show the same trajectory, cut at 50, 150, and 1,600 ns, respectively.

Binding of these ligands does not occur in a concave groove located on the surface of the receptor protein as otherwise often imagined. As described in Section 2.2.1, the x-ray structure of rhodopsin showed that retinal is bound deep in the seven-helical structure with major interaction points in TM-III and TM-VI, as well as the covalent attachment point in TM-VII. In fact, rhodopsin interacts with basically all transmembrane segments. Importantly, side-chains from the transmembrane helices cover the retinal molecule on all sides, and its binding site is found deep in the middle of... 

Schadel, SA, Heck, M, Maretzki, D, Filipek, S, Teller, DC, Palczewski, K, and Hofmann, KP, 2003. Ligand channeling within a G-protein-coupled receptor—The entry and exit of retinals in native opsin. J Biol Chem 278, 24896-24903. 

Drescher, U., Kremoser, C., Handwerker, C. et al. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82 359-370,1995. 

Notably, only part of the aromatic cluster is conserved in rhodopsin where the ligand (retinal) is covalently attached to the receptor. Thus, the 6.52 position is not needed to function as a ligand-sensor, as the conserved W6.48(265) is restrained in the... 

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