Retinylidene chromophore hydrolysis from mammalian visual and non-visual opsins

J Biol Chem. 2024 Mar;300(3):105678. doi: 10.1016/j.jbc.2024.105678. Epub 2024 Jan 23.

Abstract

Rhodopsin (Rho) and cone opsins are essential for detection of light. They respond via photoisomerization, converting their Schiff-base-adducted 11-cis-retinylidene chromophores to the all-trans configuration, eliciting conformational changes to activate opsin signaling. Subsequent Schiff-base hydrolysis releases all-trans-retinal, initiating two important cycles that maintain continuous vision-the Rho photocycle and visual cycle pathway. Schiff-base hydrolysis has been thoroughly studied with photoactivated Rho but not with cone opsins. Using established methodology, we directly measured the formation of Schiff-base between retinal chromophores with mammalian visual and nonvisual opsins of the eye. Next, we determined the rate of light-induced chromophore hydrolysis. We found that retinal hydrolysis from photoactivated cone opsins was markedly faster than from photoactivated Rho. Bovine retinal G protein-coupled receptor (bRGR) displayed rapid hydrolysis of its 11-cis-retinylidene photoproduct to quickly supply 11-cis-retinal and re-bind all-trans-retinal. Hydrolysis within bRGR in native retinal pigment epithelium microsomal membranes was >6-times faster than that of bRGR purified in detergent micelles. N-terminal-targeted antibodies significantly slowed bRGR hydrolysis, while C-terminal antibodies had no effect. Our study highlights the much faster photocycle of cone opsins relative to Rho and the crucial role of RGR in chromophore recycling in daylight. By contrast, in our experimental conditions, bovine peropsin did not form pigment in the presence of all-trans-retinal nor with any mono-cis retinal isomers, leaving uncertain the role of this opsin as a light sensor.

Keywords: 11-cis-retinal; all-trans-retinal; chromophore; retinal hydrolysis; visual cycle.

MeSH terms

  • Animals
  • Cattle
  • Cone Opsins*
  • Hydrolysis
  • Opsins* / chemistry
  • Retinaldehyde / chemistry
  • Retinoids*
  • Rhodopsin

Substances

  • Cone Opsins
  • Opsins
  • Retinaldehyde
  • Retinoids
  • retinylidene chromophore
  • Rhodopsin