Mechanism of P4-ATPase catalyzed lipid transport
P4-ATPases are lipid-transporting proteins belonging to the superfamily of P-type ATPases, a group of integral membrane pumps mainly involved in cation transport. Although P4-ATPases present high sequence similarity to other members of the P-type family, they also show remarkable differences, especially with respect to the amino acid residues involved in substrate binding.
Although this may suggest an adaptation to accomplish lipid translocation, it is not known how these proteins are able to move such large molecules as the phospholipids from one side of the membrane to the other.
Our research questions are: How are lipids transported by P4-ATPases? Which amino acid residues are involved in lipid binding? Do phospholipids get fully embedded in a central pocket in the structure of P4-ATPases or do the fatty acid chains stay out of the protein and always in contact with the hydrophobic bilayer?
We are aiming at answering these questions through a range of biochemical and biophysical approaches.
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