Rhodopsin receptor

Metal chelation has also been applied in studies of the structural-functional basis for seven-trans-membrane receptor activation. Using the (i2-adrenergic receptor as a model system, Filing el al. introduced several point mutations to form a metal binding site between trans-membrane helices III, VI and VII and showed that the receptor could be activated by metal ions alone or metal ions chelated by phenanthroline or bipyridine.1391 Based on a homology model built over the rhodopsin receptor crystal structure, helices III, VI and VII would have to move inwards to form a metal chelation site, suggesting that movement of these helices is critical for receptor activation. 

The G-proteins are heterotrimers made of three families of subunits, a, P, and y, which can interact specifically with discrete regions on G-protein-coupled receptors. This includes most receptors for neurotransmitters and polypeptide hormones (see Neuroregulators). G-protein-coupled receptors also embrace the odorant receptor family and the rhodopsin-linked visual cascade. 

Given the difficulty of obtaining three-dimensional crystals of membrane proteins, it is not surprising that the electron microscope technique is now widely used to study large membrane-bound complexes such as the acetylcholine receptor, rhodopsin, ion pumps, gap junctions, water channels and light-harvesting complexes, which crystallize in two dimensions. 

E. G protein-conpled receptors /3-Adrenergic receptor kinase (BARK) Rhodopsin kinase II. Ser/Thr/Tyr protein kinases MAP kinase kinase (MAPK kinase) —TEY— phosphorylation by... 

The four mammalian ARs are members of the rhodopsin-like Class A family of GPCRs, which contain seven transmembrane helical domains ( TMs). Character istics of the four subtypes of the human ARs, length of their primary sequences, their chromosomal localization, and their signaling pathways are given in Table 1. The A2a receptor is considerably longer than the other three subtypes, due to its extended carboxy-terminal. 

Neurokinin-1 Receptor. A homology model of the neurokinin-1 (NKi) receptor was built from the X-ray structure of rhodopsin, using the MOBILE (modeling binding sites including ligand information explicitly) approach. In this procedure, a preliminary model is generated, which is afterwards refined... 

Figure 3.3 Molecular structure of G-protein-coupled receptors. In (a) the electron density map of bovine rhodopsin is shown as obtained by cryoelectron microscopy of two-dimensional arrays of receptors embedded in lipid membrane. The electron densities show seven peaks reflecting the seven a-helices which are predicted to cross the cell membrane. In (b) is shown a helical-wheel diagram of the receptor orientated according to the electron density map shown in (a). The diagram is seen as the receptor would be viewed from outside the cell membrane. The agonist binding pocket is illustrated by the hatched region between TM3, TM5 and TM6. (From Schertler et al. 1993 and Baldwin 1993, reproduced from Schwartz 1996). Reprinted with permission from Textbook of Receptor Pharmacology. Eds Foreman, JC and Johansen, T. Copyright CRC Press, Boca Raton, Florida...

All rhodopsin-like G-protein-coupled receptors have a conserved arginine residue at the intracellular end of TM3 and this residue is thought to be crucial for G-protein activation. The third intracellular loop determines the class of G-protein activated by the receptor with the second intracellular loop and C-terminus also influencing G-protein binding in some cases. Four classes of G-protein are known ... 

By far the most studied family of the G-protein-coupled receptors are the rhodopsin-like receptors. These are also the largest group of receptors in number as they include receptors not only for the monoamines, nucleotides, neuropeptides and peptide hormones, but they also include the odorant receptors which number several hundreds of related receptors. These receptors have short N-termini, a conserved disulphide bridge between the TM2-TM3 and TM4—TM5 extracellular domains, and variable-length C-termini. In some cases the C-terminus is myristolyated which by tying the C-terminus to the cell membrane generates a fourth intracellular loop. 

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