In rhodopsin

In rhodopsin, EPR studies have demonstrated a clear helical periodicity in most of intracellular loop-3, except for a couple of residues in the middle (indicated in Figure 2.5). This would suggest that TM-V and TM-VI extend way into the cytosol and that only a very short loop connects these two helical extensions. However, in the three-dimensional crystals, most of intracellular loop-3 is a rather unstructured loop. Thus, in this case, it is likely that the EPR studies tell us something about the solution structure of the receptor, which may not be clear in the x-ray structure. 

Migani A, Sinicropi A, Ferr N, Cembran A, Garavelli M, Olivucci M (2004) Structure of the intersection space associated with Z/E photoisomerization of retinal in rhodopsin proteins. Faraday discuss 127 179... 

Mutations in rhodopsin and other photoreceptor proteins are linked to retinitis pigmentosa 814... 

Mutations in rhodopsin and other photoreceptor proteins are linked to retinitis pigmentosa. Retinitis pigmentosa (RP) is a group of inherited retinopathies that affects about 1 in 4,000 humans [26], RP maybe classified into four types autosomal dominant (19%), autosomal recessive (19%),X-linked (8%) and allied diseases (54%). RP is characterized by loss of night vision in the early stage, followed by loss of peripheral vision. Chromosomal loci for numerous RP genes have been mapped and mutations characterized [27]. 

Okada, T., Fujiyoshi, Y., Silow, M., Navarro, J., Landau, E. M. and Shichida, Y. Functional role of internal water molecules in rhodopsin revealed by x-ray crystallography. Proc. Natl Acad. Sci. USA 99 5982-5987,2002. 

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... 

Okada, T. (2004) X-ray crystallographic studies for ligand—protein interaction changes in rhodopsin. Biochemical Society Transactions, 32, 738—741. 

The general strategy for establishing the sites of protein-chromophore interactions in rhodopsin involves introduction of selective 13 C labels at each position along the length of the retinal chromophore. 

Table 39 summarizes the isotropic chemical shifts from the 13C NMR spectra of isorhodopsin along with chemical shift data from the 9-cis PSB chloride salt. The difference in chemical shifts between isorhodopsin and the 9-cis PSB are qualitatively similar to the differences observed between rhodopsin and the 11 -cis PSB with the exception of C7, where a 4.3 ppm chemical shift difference is observed, and C12, where the difference, amounting to about 3 ppm in rhodopsin, has now vanished. 

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. 

Neidhardt, J., Barthelmes, D., Farahmand, F., Fleischhauer, J. C., and Berger, W. (2006) Different amino acid substitutions at the same position in rhodopsin lead to distinct phenotypes. Invest. Ophthalmol. Vis. Sci. 47, 1630-1635. 

The molecular event that triggers the visual process is the light-induced transformation of the 11-c form of retinal in rhodopsin to the aJi-trans form. 

Reeves, P. J., CaUewaert, N., Contreras, R. and Kho-rana, H. G. (2002). Structure and function in rhodopsin high-level expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracycUne-indudble N-acetylglucosaminyltransferase 1-negative HEK293S stable mammalian cell tine. Proc. Natl. Acad. Sci. USA 99,13419-13424. 

ATP -I- peptide <1> (<1> monophosphorylated [7] <1> containing sites phosphorylated in rhodopsin [9, 23] <1> less amount of phosphoryl group incorporation than of rhodopsin [9] <1> corresponding to the C-terminus and loop 5-6 of opsin, poor substrates, phosphorylates serine and threonine residues in each peptide [12] <1> acid-rich peptides, RK prefers acid residues localized to the C-terminal side of the serine [15, 23] <1> low catalytic efficiency of RK toward a peptide containing its major autophosphorylation site [27] <1> acidic peptides, stimulated by photo-lyzed rhodopsin, K-491 of RK participates in substrate binding [33]) (Reversibility <1> [7, 9, 12, 15, 22, 23, 27, 33, 36]) [7, 9, 12, 15, 22, 23, 27, 33, 36]... 

Cai, K. Klein-Seetharaman, J. Hwa, J. Hubbell, W.L. Khorana, H.G. Structure and function in rhodopsin Effects of disulfide cross-links in the cyto-... 

Such effects are very clearly demonstrated in the calculation of Jean [25] on a model for barrierless isomerization, intended to capture some of the essential features of isomerization in rhodopsins [17], A 25-fs pulse populates the initial state and Fig. 6 shows the decay of population of that... 

In a crystal structure47111-ds-retinal has the 12-s-cis conformation shown at the top in Eq. 23-36 rather than the 12-s-frans conformation at the center and in which there is severe steric hindrance between the 10-H and 13-CH3. Nevertheless, H-and 13C-NMR spectroscopy suggest that the retinal in rhodopsin is in a twisted 12-s-frans conformation.472 4723 The Schiff base of 11-ds-retinal with N-butylamine has an absorption maximum at -360 nm but N-protonation, as in the structure in Eq. 23-36, shifts the maximum to 440 nm with emax = 40,600 M 1 cm 1 (Fig. 23-42). This large shift in the wavelength of the absorption maximum (the opsin shift) indicates that binding to opsin stabiliz-... 

The retinal Schiff base chromophore is embedded in rhodopsin with its transition dipole moment parallel to the plane of the discs, i.e., perpendicular to the direction of travel of the incoming photons. Absorption of a photon leads to a sequence of readily detectable spectral changes.37,46113,499,500 The relaxation times indicated in Eq. 23-37 are for 20°C. 

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