BPS2026 – Unravelling rapid kinetics driving human daylight vision

Photopic vision allows for high visual acuity, rapid motion detection, and color perception in daylight, enabling organisms to navigate their surroundings effectively. It is mediated by specialized G protein-coupled receptors known as cone opsins, found in photoreceptor cells in the retina. Humans possess three types of cone opsins, which are classified based on their spectral sensitivity to short- (OPN1SW), medium- (OPN1MW), and long- (OPN1LW) wavelengths. Although they have distinct spectral properties, all mammalian opsins share the same chromophore, vitamin A derivative, 11- cis -retinal. Upon photon absorption, the chromophore isomerizes to all- trans -retinal, thereby initiating the visual cascade. Dysfunction of these opsins can result in conditions such as cone-rod dystrophy, achromatopsia and color blindness, all of which might impair vision. Despite their biological and therapeutic relevance, the molecular mechanisms underlying their spectral properties and rapid activation kinetics remain largely unknown. Here, we combined structural biology approaches with time-resolved femtosecond-resolution spectroscopy and functional assays to study the two most divergent human cone opsins, OPN1SW and OPN1MW. These results reveal unique chromophore stabilization mechanisms and molecular features enabling rapid signal transduction via coupling with the transducin G protein. We further describe the photoactivation cascade and characterize rapid photoresponse kinetics, demonstrating important differences from well-studied bovine rhodopsin. Our findings provide a foundation for understanding human daylight vision, advancing vision restoration strategies and optogenetics.