Cryo-EM structure of the ATP11C Q79E mutant reveals the structural basis for altered Phospholipid recognition.

ABSTRACT: Closely related P4-ATPases, ATP11A and ATP11C, act as major phospholipid flippases in the plasma membrane of mammalian cells, with strict substrate specificity for phosphatidylserine (PS) and phosphatidylethanolamine (PE), but not for phosphatidylcholine (PC), thereby contributing to the asymmetric distribution of PS and PE across bilayers. A previously reported disease-associated Q84E mutation in ATP11A confers the ability to flip PC, implicating the involvement of this conserved residue in substrate specificity. We performed cryo-EM analysis for the equivalent mutant Q79E of ATP11C to address the structural basis for its unusual substrate specificity. Measurement of ATPase activity revealed that the ATP11C Q79E mutant retained PS-dependent activity, whilst gaining robust PC-dependent act

SUBMITTER: Qian Y 

PROVIDER: S-EPMC12723151 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature