Structure-function relationship of retinal guanylyl cyclase, a key enzyme in phototransduction

Light adaptation is the ability of visual system to adjust its performance to the ambient level of illumination. It is fundamentally vital for the normal functioning of the visual system. During the normal cycle of day and night, the illumination of the earth’s surface varies over 11 orders of magnitude. The daily cycle of sensitivity adjustment is managed by switching between rod and cone pathways of retina. These pathways involve retinal guanylyl cyclase (retGC), an enzyme encoded by the GUCY2D gene expressed in rod and cone photoreceptors. In the light-induced signal cascade, retGC restores cGMP levels in the dark in a calcium-dependent manner. Mutations in GUCY2D are associated with recessive Leber congenital amaurosis-1 (LCA1) as well as dominant and recessive forms of cone-rod dystrophy (CORD). Presently, the molecular structure of retinal GC has not been determined; thus, its mechanism, interaction with other regulators, and identity of crucial residues conferring the activity of this enzyme have been elusive. We aim to fill this gap in our knowledge by determining the molecular structure of retGC. This information will enhance our understanding of the role of retGC in photoreceptors and diseases.