Activation by rhodopsin

Zhukovsky, E. Robinson, P. Oprian, D. (1991) Transducin activation by rhodopsin without a covalent bond to the 11-cis-retinal chromophore Science, vol. 251, pp 558-559... 

Garcia, P. D., Onrust, R., Bell, S. M., Sakmar, T. P., Bourne, H. R. Transducin-alpha C-terminal mutations prevent activation by rhodopsin Anew assay using recombinant proteins expressed in cultured cells. EMBO J., 1995, 14, 4460-4469. 

To further understand the molecular mechanism of hght absorption and G protein activation by rhodopsin, it is important to determine structural changes in the bleaching process of rhodopsin at atomic resolution. Recent success of the preparation of the rhodopsin crystal enables us to determine the crystal structure of the intermediates upon irradiation of the crystal at adequate temperature. ... 

Therefore, we will be in a stage that mechanisms of photon absorption and G protein activation by rhodopsin will be elucidated at atomic resolution. 

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 ... 

Brown MF, Salgado GFJ, Struts AV (2010) Retinal dynamics during light activation of rhodopsin revealed by solid-state NMR spectroscopy. BBA-Biomembranes 1798 177-193... 

Receptors that remain in the activated state even in the absence of ligand are often known as constitutively active mutants (CAMs). The resulting disruptions in rhodopsin signaling also often result in alterations in the phosphorylation of rhodopsin by rhodopsin kinase (GRKl), the specialized GRK enzyme expressed in the retina that is largely responsible for rapidly desensitizing the receptor when it is exposed to light. 

The Gt- and Gg-proteins are also classed as Gi-proteins, based on sequence homologies. The Gt- and Gg-proteins are involved in transmitting sensory signals. Signal transmission in the vision process is mediated via G-proteins known as transducins (Gt). The Gt-proteins are activated by the photoreceptor rhodopsin and are located in the rods and cones of the retina. The sequential effector molecules of the Gt-proteins are cGMP-specific phosphdiesterases (see Fig. 17.9). 

Another regulatory Ca receptor is recoverin, which performs an important control function in the signal transduction cascade of the vision process, by inhibiting the activity of rhodopsin kinase (see Chapter 5.3.4). 

S ATP -I- 338-SKTETSQVAPA-348 <1, 12> (<1, 12> peptide containing the last 11 amino acids of the C-terminal of bovine rhodopsin [20, 24] <1> phosphorylated at Ser-343, about 11% of the rate with rhodopsin, photo-activated rhodopsin-dependent, soluble active kinase catalyzes photoacti-vated rhodopsin-independent peptide phosphorylation [20] <12> only in the presence of photoactivated rhodopsin, which activates RK for peptide phosphorylation, also activated by metarhodopsin III, but not by opsin, up to 60% of the rate with photoactivated rhodopsin, light-dependent phosphorylation [24]) (Reversibility <1,12> [20,24]) [20, 24]... 

Kikkawa, S. Yoshida, N. Nakagawa, M. Iwasa, T. Tsuda, M. A novel rhodopsin kinase in Octopus photoreceptor possesses a pleckstrin homology domain and is activated by C protein y-subunits. J. Biol. Chem., 273, 7441-7447 (1998)... 

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. 

In the structure of rhodopsin one can differentiate several groups of amino acids called microdomains. They were found to be conserved among nearly all GPCRs because they are necessary for these receptors either to take the proper shape or to function properly (to be activated by the ligand, or light in case of rhodopsin, but not spontaneously).22 The microdomains are shown on Figure 11-2 on the structure of rhodopsin. Microdomain DRY (ERY in case of rhodopsin) located on helix III and NPxxY, located on helix VII, are responsible for activation process of GPCRs. 

Filipek S, Krzysko KA, Fotiadis D, Liang Y, Saperstein DA, Engel A, Palczewski K (2004) A concept for G protein activation by G protein-coupled receptor dimers die transducin/rhodopsin interface. Photochemical Photobiological Sciences 3(6) 628—638... 

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