Flippase

Flippases are transmembrane lipid transporter proteins located in the cell membrane. They are responsible for aiding the movement of phospholipid molecules between the two layers, or leaflets, that comprise the membrane. This is called transverse diffusion, also known as "flip-flop" transition. Flippases move lipids to the cytosolic layer, usually from the extracellular layer. Floppases do the opposite, moving lipids to the extracellular layer. Both flippases and floppases are powered by ATP hydrolysis and are either P4-ATPases or ATP-Binding Cassette transporters. Scramblases are energy-independent and transport lipids in both directions.

Flippases are transmembrane lipid transporter proteins located in the cell membrane. They are responsible for aiding the movement of phospholipid molecules between the two layers, or leaflets, that comprise the membrane. This is called transverse diffusion, also known as "flip-flop" transition. Flippases move lipids to the cytosolic layer, usually from the extracellular layer. Floppases do the opposite, moving lipids to the extracellular layer. Both flippases and floppases are powered by ATP hydrolysis and are either P4-ATPases or ATP-Binding Cassette transporters. Scramblases are energy-independent and transport lipids in both directions.

Mechanism of P4-type flippases

To bind specific lipid on the outer layer of membrane, P4-type flippase needs to be phosphorylated by ATP on its P-domain. After ATP hydrolysis and phosphorylation, P4-type flippases undergo conformational change from E1 to E2 (E1 and E2 stand for different conformations of flippases). Further conformational change is induced by the binding of a phospholipid, resulting in the E2Pi.PL conformation. The flippase in its E2 conformation can then be dephosphorylated at its P-domain, allowing the lipid to be transported to the inner layer of membrane, where it diffuses away from the flippase. As the phospholipid dissociates from the complex, a conformational change on flippase occurs from E2 back to E1 readying it for the next cycle of lipid transportation. The A-domain binds to the N-domain after that domain releases ADP. The A-domain can bind to the N-domain by a TGES four-amino-acid motif when the P-domain is phosphorylated. The release of ADP from the N-domain transitions the complex from the E1P-ADP state to the E2P state, which might be further stabilized by binding of the C-terminal regulatory domain. Binding of a phospholipid to the first two transmembrane segments induces a conformational change that rotates the A domain outward by 22 degrees, allowing dephosphorylation of the P domain. Dephosphorylation of the P-domain is energetically coupled to translocation of the polar phospholipid head across the membrane leaflets.

See also

Scramblase

References

Text derived from https://en.wikipedia.org/w/index.php?oldid=1366621381 under CC BY-SA 4.0; modifications have been made.