TY - JOUR TI - Molecular structures of the eukaryotic retinal importer ABCA4 AU - Liu, Fangyu AU - Lee, James AU - Chen, Jue A2 - Drew, David A2 - Boudker, Olga A2 - Drew, David A2 - Beis, Konstantinos VL - 10 PY - 2021 DA - 2021/02/19 SP - e63524 C1 - eLife 2021;10:e63524 DO - 10.7554/eLife.63524 UR - https://doi.org/10.7554/eLife.63524 AB - The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import). ABCA4 is a eukaryotic importer transporting retinal to the cytosol to enter the visual cycle. It also removes toxic retinoids from the disc lumen. Mutations in ABCA4 cause impaired vision or blindness. Despite decades of clinical, biochemical, and animal model studies, the molecular mechanism of ABCA4 is unknown. Here, we report the structures of human ABCA4 in two conformations. In the absence of ATP, ABCA4 adopts an outward-facing conformation, poised to recruit substrate. The presence of ATP induces large conformational changes that could lead to substrate release. These structures provide a molecular basis to understand many disease-causing mutations and a rational guide for new experiments to uncover how ABCA4 recruits, flips, and releases retinoids. KW - ABC transporter KW - retinal disease KW - cryo-EM JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -