Specificity of the chromophore-binding site in human cone opsins

The variable composition of the chromophore-binding pocket in visual receptors is essential for vision. The visual phototransduction starts with the cis-trans isomerization of the retinal chromophore upon absorption of photons. Despite sharing the common 11-cis-retinal chromophore, rod and cone phot...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 294; no. 15; pp. 6082 - 6093
Main Authors:	Katayama, Kota, Gulati, Sahil, Ortega, Joseph T., Alexander, Nathan S., Sun, Wenyu, Shenouda, Marina M., Palczewski, Krzysztof, Jastrzebska, Beata
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 12-04-2019 American Society for Biochemistry and Molecular Biology
Subjects:	11-cis-6mr-retinal Cone Opsins - chemistry Cone Opsins - genetics Cone Opsins - metabolism G protein-coupled receptor (GPCR) HEK293 Cells Humans membrane protein Models, Molecular Molecular Biophysics photoreceptor Protein Binding protein structure retinal pigment Retinaldehyde - chemistry Retinaldehyde - metabolism retinoid rhodopsin vision rhodopsin protein structure vision 11-cis-6mr-retinal photoreceptor G protein-coupled receptor (GPCR) membrane protein retinal pigment retinoid
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Summary:	The variable composition of the chromophore-binding pocket in visual receptors is essential for vision. The visual phototransduction starts with the cis-trans isomerization of the retinal chromophore upon absorption of photons. Despite sharing the common 11-cis-retinal chromophore, rod and cone photoreceptors possess distinct photochemical properties. Thus, a detailed molecular characterization of the chromophore-binding pocket of these receptors is critical to understanding the differences in the photochemistry of vision between rods and cones. Unlike for rhodopsin (Rh), the crystal structures of cone opsins remain to be determined. To obtain insights into the specific chromophore–protein interactions that govern spectral tuning in human visual pigments, here we harnessed the unique binding properties of 11-cis-6-membered-ring-retinal (11-cis-6mr-retinal) with human blue, green, and red cone opsins. To unravel the specificity of the chromophore-binding pocket of cone opsins, we applied 11-cis-6mr-retinal analog-binding analyses to human blue, green, and red cone opsins. Our results revealed that among the three cone opsins, only blue cone opsin can accommodate the 11-cis-6mr-retinal in its chromophore-binding pocket, resulting in the formation of a synthetic blue pigment (B6mr) that absorbs visible light. A combination of primary sequence alignment, molecular modeling, and mutagenesis experiments revealed the specific amino acid residue 6.48 (Tyr-262 in blue cone opsins and Trp-281 in green and red cone opsins) as a selectivity filter in human cone opsins. Altogether, the results of our study uncover the molecular basis underlying the binding selectivity of 11-cis-6mr-retinal to the cone opsins.
Bibliography:	Edited by Wolfgang Peti Both authors made equal contributions to this work.
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.RA119.007587