Seven Transmembrane Helix Receptors

Seven transmembrane helix receptors Heptahelical receptors Serpentine receptors... 

Great excitement has been generated in the signal transduction field by the first determination of the structure of a seven-transmembrane-helix receptor—the visual system protein rhodopsin—discussed in Chapters 15 and ... 

We begin by considering the largest and one of the most important classes of receptor, the seven-transmembrane-helix receptors. 

Seven-Transmembrane-Helix Receptors Change Conformation in Response to Ligand Binding and Activate G Proteins... 

Seven-transmembrane-helix receptors operate in conjunction with heterotrimeric G proteins. The binding of hormone to a 7TM receptor triggers the exchange of GTP for GDP bound to the a subunit of the G protein. G proteins can transmit... 

Olfaction Is Mediated by an Enormous Family of Seven-Transmembrane-Helix Receptors... 

Oliveira, L., Paiva, A. C. M., Vriend, G. A common motif in G-protein-coupled seven transmembrane helix receptors. J. Computer-Aided Mol. Design, 1993, 7, 649-658. 

What essential feature is carried out by the seven-transmembrane-helix receptors (7TM) ... 

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. 

G-Protein coupled receptors (GPCR) represent the start element in secondary messenger producing systems. They comprise a family of over 1000 structurally-related members. These membrane proteins are also called serpentine or seven-helix receptors due to their seven transmembrane domains with an a-helical conformation. Receptors belonging to this class respond to a variety of hormones and neurotransmitters, and they detect odorant molecules or light [3,4]. 

Receptors and their ligands are numerous, varied, and essential to all forms of life. Cell-surface receptors on bacteria detect feeding attractants as well as dangerous molecules. From bacteria to humans seven-helix receptors function to detect light, odors, hormones, and other molecules. Tire numbers of different receptors are impressive. For example, the tiny nematode C. elegans has 650 seven-helix transmembrane receptors and 411 protein kinases, many of which may be associated with receptors.34 Our bodies have thousands. 

Fig. 2. Structure of a heptahelical receptor. Cartoon model of dark (inactive) bovine rhodopsin (1U19), showing the seven transmembrane-spanning a helices (red to blue) and 11-r/Vi ctinal (gray spheres). Conserved residues important for receptor and G protein activation are shown (magenta spheres), including the DRY motif on helix III (yellow) and NpxxYx5F motif on helices VII and VIII blue and purple). The extracellular and intracellular faces of rhodopsin are shown. Receptor activation results in an outward movement of helix VI yellow arrow), which opens a gap in the cytoplasmic face of the receptor, exposing residues critical for G protein activation, such as the DRY motif on helix III (yellow).

It has been known for a long time that the skeletal muscle L-type calcium channel complex also contains a y subunit - a four transmembrane helix with cytoplasmic bland C-termini (Arikkath and Campbell 2003). Seven additional potential candidates for neuronal calcium channel y subunits have been identified however, it is not clear if these are bona fide calcium channel subunits. Indeed, the first identified neuronal calcium channel y subunit stargazin has also been linked to AMPA receptor trafficking and pharmacology (Chen et al. 2000 Tomita et al. 2005). Hence, it remains unclear to what extent these subunits associate with the calcium channel complex in neurons. 

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