A human opsin-related gene that encodes a retinaldehyde-binding protein

Area of Science:

• Biochemistry
• Molecular Biology
• Ophthalmology

Background:

• The retinal pigment epithelium (RPE) plays a crucial role in the visual cycle.
• G protein-coupled receptors (GPCRs) are involved in signal transduction in various tissues, including the eye.

Purpose of the Study:

• To characterize the ligand-binding properties of a novel protein from bovine RPE.
• To investigate the structural and evolutionary relationship of this protein to other opsins.
• To explore potential functions of the identified receptor.

Main Methods:

• Demonstration of ligand-binding properties of the bovine RPE protein.
• Amino acid sequence comparison between bovine and human RGR.
• Analysis of the human RGR gene structure and alternative splicing.
• Sodium borohydride reduction assay for retinal binding.

Main Results:

• A 32-kDa cytoplasmic membrane-bound protein, RPE-retinal G protein coupled receptor (RGR), was identified.
• RGR covalently binds both all-trans- and 11-cis-retinal, with a preference for all-trans-retinal.
• Human RGR shares 86% amino acid identity with bovine RGR, with conserved key residues.
• The human RGR gene structure is distinct from visual pigment genes, suggesting an early evolutionary origin.
• Alternative splicing generates a second human RGR variant with an amino acid insertion.

Conclusions:

• The RPE-retinal G protein coupled receptor (RGR) binds retinaldehyde, preferentially all-trans-retinal.
• RGR represents an early branch of the vertebrate opsin gene family.
• A potential function of RGR is the isomerization of the chromophore, possibly via a retinochrome-like mechanism.