Advances in understanding the molecular basis of the first steps in color vision

Abstract

Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation.

A G Protein-Coupled Receptor Dimerization Interface in Human Cone Opsins

“…39 The wavelength of maximal absorbance of red cone opsin is 564 nm, just 30 nm longer than the maximal absorbance wavelength of green cone opsin, 534 nm. 39 Moreover, red and green cone opsin amino acid sequences are identical except for 15 residues. On the basis of functional mutagenesis work, the spectral distinction between red and green cone opsins distributed over precisely seven of those amino acid residues.…”

“…For example, the lipid content of rod and cone membrane disks differs notably from that of the plasma membrane of Cos-7 cells, 70 and the density range studied here is 2–3 orders of magnitude lower than the actual physiological densities. 39 So, what physiological relevance could there be for red cone opsin dimerization? One possibility could be to stabilize the protein by reducing the effect of thermal fluctuations on receptor activation.…”

Hydrogen/Deuterium Exchange Mass Spectrometry of Human Green Opsin Reveals a Conserved Pro-Pro Motif in Extracellular Loop 2 of Monostable Visual G Protein-Coupled Receptors

“…48 Raw data in the form of the relative signal intensity (percent) as a function of m / z were extracted with Xcalibur version 2.1.0. Qual Browser was used for a recently described semiautomated peak detection, and a deconvolution procedure was performed with HX-Express 2 . 49 The extent of H/D exchange was color-coded on the basis of the total percent of the theoretical maximal deuterium uptake at 10 min as follows: dark blue for 0–4%, light blue for 5–9%, cyan for 10–14%, cadet blue for 15–19%, green for 20–24%, light green for 25–29%, yellow for 30–34%, orange for 35–39%, and red for 40–44%.…”

“…1,2 The four opsins in the human retina [rhodopsin, short wavelength sensitive 1 (SWSl) opsin, medium wavelength sensitive 1 (M/LWS) opsin, and long wavelength sensitive 1 (L/LWS) opsin] differ in their spectral absorbance, sensitivity, regeneration kinetics, and regulation of downstream signaling. 3,4 All four pigments are activated by the isomerization of the chromophore 11- cis -retinal to all- trans -retinal, which is then released and regenerated back to 11- cis -retinal through the retinoid cycle.…”

Single cell RNA-seq reveals cellular diversity and developmental characteristics of human infant retina

“…Based on previous study, there are three types of cone photoreceptors in human retina that can be differentiated by the expression of three opsins (OPN1SW, OPN1MW, OPN1LW), responsible for the perception of colors with different wavelengths 15,16 . To assess the heterogeneity of cone, we performed reclustering in cone PR clusters and divided them into 3 subclusters (Figure 3a).…”