Isomerization rhodopsins

Polli D, Altoe P, Weingart O, Spillane KM, Manzoni C, Brida D, Tomasello G, Orlandi G, KukuraP, Mathies RA, Garavelli M, Cerullo G (2010) Rhodopsin isomerization probed in the visible spectral range. Nature 467 440-443... 

Our ability to see depends in part on an interconversion of cis and trans isomers that takes place in our eyes. A protein called opsin binds to cA-retinal (formed from vitamin A) in photoreceptor cells (called rod cells) in the retina to form rhodopsin. When rhodop-sin absorbs light, a double bond interconverts between the cis and trans configurations, triggering a nerve impulse that plays an important role in vision. fran -Retinal is then released from opsin. trawi-Retinal isomerizes back to cA-retinal and another cycle begins. To trigger the nerve impulse, a group of about 500 rod cells must register five to seven rhodopsin isomerizations per cell within a few tenths of a second. 

Schoenlein R W, Peteanu LA, Mathies R A and Shank C V 1991 The first step in vision femtosecond isomerization of rhodopsin Sc/ence 254 412-15... 

Metarhodopsin 11 is then recycled back into rhodopsin by a multistep sequence involving cleavage to all-traws-retinal and cis-trans isomerization back to 11-ris-retinal. 

FIGURE 7.16 (A) Photocurrents of salamander rod cells following light flashes giving between 10 and 2000 rhodopsin molecule isomerizations. (B) Calculated increments in phosphodiesterase hydrolytic rate constant. (From Lamb, T. D. and Pugh, Jr., E. N., Trends Neurosci., 15, 291-299, 1992. With permission.)... 

Bleaching is reversed in the dark and the red-purple color of rhodopsin returns. This is thought to occur by the reduction of all-Pms-retinal to vitamin Ai (retinal), which diffuses from the rod into the pigment epithelium, where it is converted enzymatically to the 1 l-c isomer of vitamin At. The enzymatic isomerization is followed by diffusion back into the rod, oxidation to 11 -rfr-retinal, and combination with opsin to form rhodopsin. This process is shown schematically in Figure 12.5.[Pg.289]

Intriguingly, the conical intersection model also suggests that E,Z-isomerization of acyclic dienes might be accompanied by conformational interconversion about the central bond, reminiscent of the so-called Hula-Twist mechanism for the efficient ,Z-photo-isomerization of the visual pigment rhodopsin in its rigid, natural protein environment101. A study of the photochemistry of deuterium-labelled 2,3-dimethyl-l,3-butadiene (23-d2) in low temperature matrices (vide infra) found no evidence for such a mechanism in aliphatic diene E,Z -photoisomerizations102. On the other hand, Fuss and coworkers have recently reported results consistent with the operation of this mechanism in the E,Z-photoisomerization of previtamin D3 (vide infra)103. 

The study of the mechanism of vision in vertebrates 23>24) has progressed to the point where the first consequence of photon absorption has been described as an activation of the isomerization of the 11 -cis retinal chromophore of rhodopsin to all-trans. That triggers a complex sequence of reactions leading to the mysterious inside of the brain. Brrr, I had better get back — it looks dark in there. But the brain can generate sensations of light. Maybe, one day, we will be able to see enough to understand, but we ll go back just the same to a safer subject. 

A deficiency of vitamin A leads to vision defects, including a visual impairment at low light levels, termed night blindness. For the processes of vision, retinol needs to be converted first by oxidation into the aldehyde retinal, and then by enzymic isomerization to cw-retinal. c -Retinal is then bound to the protein opsin in the retina via an imine linkage (see Section 7.7.1) to give the red visual pigment rhodopsin. 

When light strikes the rod cells, isomerization of the C-ll/C-12 double bond takes place, and tra 5 -rhodopsin (metarhodopsin II) is formed. This cis-trans isomerization is accompanied by an alteration in molecular geometry, which generates a nerve impulse to be sent to the brain, resulting in the perception of vision. Metarhodopsin II is recycled back to rhodopsin by a multi-step sequence that involves the cleavage to all-trani-retinal and cis-trans isomerization back to 11-cA-retinal. 

Photochemical cis-trans isomerization in a conjugated polyene system is thought to be the crucial primary process in vision. The visual pigment (rhodopsin) is derived from 11 -crs-retinal by reaction of the aldehyde group with an amino substituent in a protein (opsin). There is considerable distortion in the geometry of this chromophoric group anyway, because of the spatial requirements of the protein... 

The Photoactive Yellow Protein (PYP) is the blue-light photoreceptor that presumably mediates negative phototaxis of the purple bacterium Halorhodospira halophila [1]. Its chromophore is the deprotonated trans-p-coumaric acid covalently linked, via a thioester bond, to the unique cystein residue of the protein. Like for rhodopsins, the trans to cis isomerization of the chromophore was shown to be the first overall step of the PYP photocycle, but the reaction path that leads to the formation of the cis isomer is not clear yet (for review see [2]). From time-resolved spectroscopy measurements on native PYP in solution, it came out that the excited-state deactivation involves a series of fast events on the subpicosecond and picosecond timescales correlated to the chromophore reconfiguration [3-7]. On the other hand, chromophore H-bonding to the nearest amino acids was shown to play a key role in the trans excited state decay kinetics [3,8]. In an attempt to evaluate further the role of the mesoscopic environment in the photophysics of PYP, we made a comparative study of the native and denatured PYP. The excited-state relaxation path and kinetics were monitored by subpicosecond time-resolved absorption and gain spectroscopy. 

A stack of about 1 000 disks in each rod cell contains the lightsensing protein rhodopsin,10 in which the chromophore 11-o i-retinal (from vitamin A) is attached to the protein opsin. When light is absorbed by rhodopsin, a series of rapid transformations releases all-frans-retinal. At this stage, the pigment is bleached (loses all color) and cannot respond to more light until retinal isomerizes back to the 11 -cis form and recombines with the protein. 

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... 

To summarize, Jean shows that coherence can be created in a product as a result of nonadiabatic curve crossing even when none exists in the reactant [24, 25]. In addition, vibrational coherence can be preserved in the product state to a significant extent during energy relaxation within that state. In barrierless processes (e.g., an isomerization reaction) irreversible population transfer from one well to another occurs, and coherent motion can be observed in the product regardless of whether the initially excited state was prepared vibrationally coherent or not [24]. It seems likely that these ideas are crucial in interpreting the ultrafast spectroscopy of rhodopsins [17], where coherent motion in the product is directly observed. Of course there may be many systems in which relaxation and dephasing are much faster in the product than the reactant. In these cases lack of observation of product coherence does not rule out formation of the product in an essentially ballistic manner. 

I and II. At very low temperatures a transient form photorhodopsin with a wavelength maximum at 580 nm may precede bathorhodopsin.461b,501-502a Furthermore, nanosecond photolysis of rhodopsin has revealed a blue-shifted intermediate that follows bathorhodopsin within 40 ns and decays into lumirhodopsin.500,503,504 The overall result is the light-induced isomerization of the bound 11-czs-retinal to all-fraus-retinal (Eq. 23-38) and free opsin. Tire free opsin can then combine with a new molecule of 11-czs-retinal to complete the photochemical cycle. 

The reaction sequence of Eq. 23-37 can be slowed by lowering the temperature. Thus, at 70K illumination of rhodopsin leads to a photostationary state in which only rhodopsin, bathorhodopsin, and a third form, isorhodopsin, are present in a constant ratio.510 Isorhodopsin (maximum absorption at 483 nm)513 contains 9-ds-retinal and is not on the pathway of Eq. 23-37. Resonance Raman spectroscopy at low temperature supports a distorted all-frans structure for the retinal Schiff base in bathorhodopsin.510 The same technique suggests the trans geometry of the C = N bond shown in Eqs. 23-38 and 23-39. Simple Schiff bases of 11-cz s-retinal undergo isomerization just as rapidly as does rhodopsin.514... 

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