For a study, researchers sought to understand that the ATP-binding cassette (ABC) transporter superfamily, which was mostly present along the rim of the disc membranes of rod and cone photoreceptors, is responsible for Stargardt macular degeneration, also known as StABCA4. The energy from ATP binding and hydrolysis was used to move the N-retinylidene-phosphatidylethanolamine (N-Ret-PE) Schiff base adduct of retinal and phosphatidylethanolamine from the lumen to the cytoplasmic leaflet of disc membranes. Harmful retinoid compounds were prevented from accumulating by ensuring that extra 11-cis-retinal and all-trans-retinal were appropriately eliminated from photoreceptor cells. Loss-of-function mutations in the ABCA4 gene were the root cause of Stargardt disease (STGD1), also known as autosomal recessive Stargardt macular degeneration, and related autosomal recessive retinopathies, which were characterized by impaired central vision and an accumulation of lipofuscin and bis-retinoid compounds. Cryo-electron microscopy was used to determine the high-resolution structures of ABCA4 in its substrate- and nucleotide-free states and with bound N-Ret-PE or ATP. These structures provided insight into the molecular structure of ABCA4, the mechanisms enabling substrate recognition, and the conformational changes induced by ATP binding. In addition, the expression and functional properties of numerous disease-causing missense ABCA4 variants had been found. Through these studies, the molecular mechanisms behind Stargardt disease have been explained, and a classification that reliably predicts the effect of a specific missense mutation on the severity of the condition has been created. They also provided a framework for rational treatment strategies for ABCA4-related diseases.

Source: sciencedirect.com/science/article/abs/pii/S1350946221000975