The lipid head group is the key element for substrate recognition by the P4 ATPase ALA2: A phosphatidylserine flippase

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Lisa Theorin, Kristina Faxén, Danny Mollerup Sørensen, Rebekka Migotti, Gunnar Dittmar, Jürgen Schiller, David L. Daleke, Michael Palmgren, Rosa Laura López-Marqués, Thomas Günther Pomorski

Type IV P-type ATPases (P4 ATPases) are lipid flippases that catalyze phospholipid transport from the exoplasmic to the cytoplasmic leaflet of cellular membranes, but the mechanism by which they recognize and transport phospholipids through the lipid bilayer remains unknown. In the present study, we succeeded in purifying recombinant aminophospholipid ATPase 2 (ALA2), a member of the P4 ATPase subfamily in Arabidopsis thaliana, in complex with the ALA-interacting subunit 5 (ALIS5). The ATP hydrolytic activity of the ALA2–ALIS5 complex was stimulated in a highly specific manner by phosphatidylserine. Small changes in the stereochemistry or the functional groups of the phosphatidylserine head group affected enzymatic activity, whereas alteration in the length and composition of the acyl chains only had minor effects. Likewise, the enzymatic activity of the ALA2–ALIS5 complex was stimulated by both mono- and di-acyl phospha-tidylserines. Taken together, the results identify the lipid head group as the key structural element for substrate recognition by the P4 ATPase.

OriginalsprogEngelsk
TidsskriftBiochemical Journal
Vol/bind476
Udgave nummer5
Sider (fra-til)783-794
ISSN0264-6021
DOI
StatusUdgivet - 6 mar. 2019

ID: 224710864