Which of the following proteins uses ATP to maintain membrane asymmetry?
Maintenance of phospholipid asymmetry across leaflets requires energy-driven transport because spontaneous flip-flop faces large kinetic barrier. Phosphatidylserine and phosphatidylethanolamine enriched inner leaflet carry negative curvature and anionic charge recruiting polybasic proteins; their headgroups contain phosphate and serine ethanolamine that cannot traverse hydrocarbon core without passing high energy transition state estimated twenty kilocalories. P4-ATPases termed flippases ATP8A1, ATP8A2, ATP11A, ATP11C hydrolyze ATP cycling through E1 to E2 conformational changes creating water-filled pathway lined by polar residues forming groove accommodating headgroup translocating lipids from outer to inner leaflet against concentration gradient maintaining inner enrichment. Floppases ABC transporters ABCB1, ABCB4 move phosphatidylcholine outward ATP dependent supporting bile secretion, scramblases TMEM16F phospholipid scramblase 1 calcium activated catalyze bidirectional nonselective mixing during platelet activation and apoptosis exposing PS as eat-me and procoagulant signal. Spectrin actin lack lipid transport activity but stabilize bilayer indirectly. Structural studies reveal credit-card like groove accommodating headgroup transport demonstrating molecular mechanism of phospholipid flipping across bilayer.
Ref: Pomorski and Menon, Lipid Flippases and Membrane Asymmetry, Annu Rev Cell Dev Biol 2016.