RT Journal Article
SR Electronic
T1 Crystal structure of a human plasma membrane phospholipid flippase
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.23.881698
DO 10.1101/2019.12.23.881698
A1 Nakanishi, Hanayo
A1 Irie, Katsumasa
A1 Segawa, Katsumori
A1 Hasegawa, Kazuya
A1 Fujiyoshi, Yoshinori
A1 Nagata, Shigekazu
A1 Abe, Kazuhiro
YR 2020
UL http://biorxiv.org/content/early/2020/01/22/2019.12.23.881698.abstract
AB ATP11C, a member of P4-ATPase flippase, exclusively translocates phosphatidylserine from the outer to the inner leaflets of the plasma membrane, and maintains the asymmetric distribution of phosphatidylserine in the living cell. However, the mechanisms by which ATP11C translocates phosphatidylserine remain elusive. Here we show the crystal structures of a human plasma membrane flippase, ATP11C-CDC50A complex, in an outward-open E2P conformation. Two phosphatidylserine molecules are in a conduit that continues from the cell surface to the occlusion site in the middle of the membrane. Mutations in either of the phosphotidylserine binding sites or along the pathway between significantly impairs specific ATPase and transport activities. We propose a model for phosphatidylserine translocation from the outer to the inner leaflet of the plasma membrane.