| ABCA7 belongs to the ATP-binding cassette subfamily A, a group of membrane transporters that actively translocate phospholipids across lipid bilayers using ATP hydrolysis. The protein features two transmembrane domains, each with six helices forming substrate tunnels, and two cytoplasmic nucleotide-binding domains that drive conformational changes for lipid extrusion. ABCA7 preferentially exports phosphatidylserine over phosphatidylcholine from the outer leaflet to the extracellular space, interacting with apolipoproteins to form lipoprotein particles that facilitate lipid efflux in a unidirectional manner, distinct from ABCA1's preference for phosphatidylcholine. The protein features two transmembrane domains, each with six helices forming substrate tunnels, and two cytoplasmic nucleotide-binding domains that drive conformational changes for lipid extrusion. ABCA7 preferentially exports phosphatidylserine over phosphatidylcholine from the outer leaflet to the extracellular space, interacting with apolipoproteins to form lipoprotein particles that facilitate lipid efflux in a unidirectional manner, distinct from ABCA1's preference for phosphatidylcholine. An open state presents a continuous lipid bilayer patch spanning the transmembrane domain for substrate entry, transitioning to a nucleotide-bound closed state that expels phospholipids through a small extracellular vestibule via rigid-body motions of the domains. These dynamics position ABCA7 at the interface of membrane asymmetry maintenance and lipid homeostasis, particularly enriching neuronal and microglial membranes, where it modulates phospholipid composition critical for synaptic integrity and vesicular trafficking. Loss-of-function variants disrupt this transport, elevating amyloid-β levels through impaired processing and reduced microglial phagocytosis, while altering mitochondrial phospholipid profiles that underpin energy metabolism in brain cells. |
Lane 1: Mouse brain, Lane 2: Mouse lung, Lane 3: Mouse spleen
