Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
This is a member of a family of an ATP-Binding Cassette or ABC transporter proteins. The membrane protein has 12 transmembrane helices.In contrast to other ion transporters which transport a discrete number of ions (3 sodium and 2 potassium ions, for example), this changes conformation to form an open pore through which chloride ions flow.This protein is defective in Cystic Fibrosis.
Multidrug Resistance Transporter - MDR
This is another example of an ATP-Binding Cassette or ABC transporter.It acts in a somewhat promiscuous fashion in pumping nonpolar toxic molecules out of the cell.This would seem quite beneficial to the organism, unless the toxic molecule is a chemotherapeutic drug used to kill a tumor cell.
- Jmol: EmrE multidrug resistance transporter - Sci. 310, 1950 (2005)
Phospholipid Flippase or Transbilayer amphipath transporter (TAT)
This is a member of theP-Type ATPase family which instead of moving ions across the membrane flips amino lipids (like PE) across leaflets in the bilayer.In an early chapter we noted that flip-flop diffusion in liposomes was slow compared to that in cells, suggesting that the flip-flop diffusion was catalyzed in the cell.Catalysis requires ATP cleavage and produces two conformations of the protein.During the conformational change of the protein, a phospholipid appears to bind to the protein and is flipped to the other side ofthe membrane.
The disposition of phosphatidylserine, a negatively charged phospholipid,between membrane leaflets is especially interesting and import.Almost all the PS is localized in the inner leaflet.Cells in which PS is found in the outer leaflet are target for program cell death (apoptosis).PS in the outer leaflet can also promote blood clotting as clotting factors are recruited to the surface.It appears that a P-type ATPase is required.Using gene silencing by RNA interference inC. Elegans, Darland-Ranson found that onespecific P-type ATPase, TAT-1 out of 6 found in the organisms had PS flippase activity, which would retain PS in the inner leaflet.Cells with PS in the outer leaflet were often targets of phagocytosis, suggesting the phagocytes have receptors that recognize PS.Cells with PS receptors may also bind and internalize virus, which have membrane leaflets acquired from infected cells as the virus buds off from the cells.Such cells might have PS in their outer leaflets since the infected cells may be in the process of dying through apoptosis, which would increase PS in the outer leaflet.
Experimental Study of Flipping:Labeling new PL ; Assay for Flip-flop Diffusion