Fig. 2.

Schematic diagram of the P4-ATPase reaction cycle. Enzyme conformations and complexes are shown in boxes while substrates and binding factors are represented in circles. DGET is the P4 ATPase sequence corresponding to the TGES motif in Ca and Na/K ATPases. Insertion of the DGET/TGES loop into the site vacated by ADP is the key step in the conversion of E1~P to E2~P. Phospholipid and CDC50 subunit both interact with the E2~P conformation, but the binding sequence is not known and so both scenarios are shown. Under physiological conditions, the ATP that donates the phosphate to the E1~P intermediate may be prebound at low affinity in the E2 conformation. In the cartoon figures, the cytoplasmic side is up, and the transmembrane region corresponds to the overlap between the stems of the transporter and subunit