Disease mutations reveal residues critical to the interaction of P4-ATPases with lipid substrates.

ABSTRACT: Phospholipid flippases (P₄-ATPases) translocate specific phospholipids from the exoplasmic to the cytoplasmic leaflet of membranes. While there is good evidence that the overall molecular structure of flippases is similar to that of P-type ATPase ion-pumps, the transport pathway for the "giant" lipid substrate has not been determined. ATP8A2 is a flippase with selectivity toward phosphatidylserine (PS), possessing a net negatively charged head group, whereas ATP8B1 exhibits selectivity toward the electrically neutral phosphatidylcholine (PC). Setting out to elucidate the functional consequences of flippase disease mutations, we have identified residues of ATP8A2 that are critical to the interaction with the lipid substrate during the translocation process. Among the residues pin

SUBMITTER: Gantzel RH 

PROVIDER: S-EPMC5585164 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature