Human Cellular Retinaldehyde-Binding Protein Has Secondary Thermal 9-<i>cis</i>-Retinal Isomerase Activity

Bolze, Christin S.; Helbling, Rachel E.; Owen, Robin L.; Pearson, Arwen R.; Pompidor, Guillaume; Dworkowski, Florian; Fuchs, Martin R.; Furrer, Julien; Golczak, Marcin; Palczewski, Krzysztof; Cascella, M.; Stocker, Achim

doi:10.1021/ja411366w

Cited by 13 publications

(26 citation statements)

References 82 publications

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“…[66] 9-cis-Retinol (1a)c ould, in principle, be diverted from the equilibrium mixture generated by DES-1 by using as imilar mechanism, as the retinol binding proteins (RBPs) Ia nd II also bind and presumably transport 9-cis-retinol (1a), [67] which after oxidation leads to aldehyde 1b used by the retina cells to form isorhodopsinv isual pigments. [68] It is interesting to note that DES-1 is expressed in multiple tissues outside the eye, including brain, liver,k idney,a nd skin, and this might be the only source of 9-cis-retinol (1a)i nv ertebrates. [65] Compound 1a has previously been reported in fish liver [69] and, together with 9-cis-b,b-carotene ( 26), in human serum/tissues and in milk products.…”

Section: Enzyme Isomerase and Saturasementioning

confidence: 99%

An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!

2016

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9-cis-Retinoic acid was identified and claimed to be the endogenous ligand of the retinoid X receptors (RXRs) in 1992. Since then, the endogenous presence of this compound has never been rigorously confirmed. Instead, concerns have been raised by other groups that have reported that 9-cis-retinoic acid is undetectable or that its presence occurs at very low levels. Furthermore, these low levels could not satisfactorily explain the physiological activation of RXR. Alternative ligands, among them various lipids, have also been identified, but also did not fulfill criteria for rigorous endogenous relevance, and their consideration as bona fide endogenous mammalian RXR ligand has likewise been questioned. Recently, novel studies claim that the saturated analogue 9-cis-13,14-dihydroretinoic acid functions as an endogenous physiologically relevant mammalian RXR ligand.

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Section: Enzyme Isomerase and Saturasementioning

confidence: 99%

An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!

2016

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“…The retinoid cycle is completed by transport of 11- cis -retinal back to the photoreceptors, where it conjugates with opsin and thus regenerates visual pigment. Structures of cellular retinol-binding protein 1 (CRBP1), retinoid isomerase (RPE65) and cellular retinaldehyde-binding protein (CRALBP) correspond to PDB accession numbers 5H8T [79], 3KVC [96], and 4CIZ [97], respectively. Generic model of 11- cis -retinol dehydrogenases (11- cis -RDHs) was built based on the structure of dehydrogenase from Drosophila melanogaster PDB accession number 5ILG.…”

Section: Figurementioning

confidence: 99%

Molecular Basis for Vitamin A Uptake and Storage in Vertebrates

et al. 2016

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The ability to store and distribute vitamin A inside the body is the main evolutionary adaptation that allows vertebrates to maintain retinoid functions during nutritional deficiencies and to acquire new metabolic pathways enabling light-independent production of 11-cis retinoids. These processes greatly depend on enzymes that esterify vitamin A as well as associated retinoid binding proteins. Although the significance of retinyl esters for vitamin A homeostasis is well established, until recently, the molecular basis for the retinol esterification enzymatic activity was unknown. In this review, we will look at retinoid absorption through the prism of current biochemical and structural studies on vitamin A esterifying enzymes. We describe molecular adaptations that enable retinoid storage and delineate mechanisms in which mutations found in selective proteins might influence vitamin A homeostasis in affected patients.

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“…Cellular retinaldehyde-binding protein (CRALBP) in the RPE and Müller cells, and extracellular interphotoreceptor retinoidbinding protein (IRBP) are two major carriers involved. 16 The structure of CRALBP-with its unanticipated isomerase activity-has been elucidated, [271][272][273] whereas the structure of IRBP has only been partially characterized. 274 Inactivating mutations FIGURE 7.…”

Section: Restoration Of Photoactive Visual Pigments: the Retinoid (Vimentioning

confidence: 99%

Chemistry and Biology of the Initial Steps in Vision: The Friedenwald Lecture

Palczewski¹

2014

Invest. Ophthalmol. Vis. Sci.

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Visual transduction is the process in the eye whereby absorption of light in the retina is translated into electrical signals that ultimately reach the brain. The first challenge presented by visual transduction is to understand its molecular basis. We know that maintenance of vision is a continuous process requiring the activation and subsequent restoration of a vitamin A-derived chromophore through a series of chemical reactions catalyzed by enzymes in the retina and retinal pigment epithelium (RPE). Diverse biochemical approaches that identified key proteins and reactions were essential to achieve a mechanistic understanding of these visual processes. The three-dimensional arrangements of these enzymes' polypeptide chains provide invaluable insights into their mechanisms of action. A wealth of information has already been obtained by solving high-resolution crystal structures of both rhodopsin and the retinoid isomerase from pigment RPE (RPE65). Rhodopsin, which is activated by photoisomerization of its 11-cis-retinylidene chromophore, is a prototypical member of a large family of membrane-bound proteins called G protein-coupled receptors (GPCRs). RPE65 is a retinoid isomerase critical for regeneration of the chromophore. Electron microscopy (EM) and atomic force microscopy have provided insights into how certain proteins are assembled to form much larger structures such as rod photoreceptor cell outer segment membranes. A second challenge of visual transduction is to use this knowledge to devise therapeutic approaches that can prevent or reverse conditions leading to blindness. Imaging modalities like optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) applied to appropriate animal models as well as human retinal imaging have been employed to characterize blinding diseases, monitor their progression, and evaluate the success of therapeutic agents. Lately two-photon (2-PO) imaging, together with biochemical assays, are revealing functional aspects of vision at a new molecular level. These multidisciplinary approaches combined with suitable animal models and inbred mutant species can be especially helpful in translating provocative cell and tissue culture findings into therapeutic options for further development in animals and eventually in humans. A host of different approaches and techniques is required for substantial progress in understanding fundamental properties of the visual system.

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Human Cellular Retinaldehyde-Binding Protein Has Secondary Thermal 9-cis-Retinal Isomerase Activity

Cited by 13 publications

References 82 publications

An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!

An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!

Molecular Basis for Vitamin A Uptake and Storage in Vertebrates

Chemistry and Biology of the Initial Steps in Vision: The Friedenwald Lecture

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