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Conformational changes of a phosphatidylcholine flippase in lipid membranes.

Xu J, He Y, Wu X, Li L
Cell Rep 38 110518 (2022)
Related entries: 7drx, 7dsh, 7dsi, 7f7f, 7whw

Cited: 7 times
EuropePMC logo PMID: 35294892

Abstract

Type 4 P-type ATPases (P4-ATPases) actively and selectively translocate phospholipids across membrane bilayers. Driven by ATP hydrolysis, P4-ATPases undergo conformational changes during lipid flipping. It is unclear how the active flipping states of P4-ATPases are regulated in the lipid membranes, especially for phosphatidylcholine (PC)-flipping P4-ATPases whose substrate, PC, is a substantial component of membranes. Here, we report the cryoelectron microscopy structures of a yeast PC-flipping P4-ATPase, Dnf1, in lipid environments. In native yeast lipids, Dnf1 adopts a conformation in which the lipid flipping pathway is disrupted. Only when the lipid composition is changed can Dnf1 be captured in the active conformations that enable lipid flipping. These results suggest that, in the native membrane, Dnf1 may stay in an idle conformation that is unable to support the trans-membrane movement of lipids. Dnf1 may have altered conformational preferences in membranes with different lipid compositions.

Reviews citing this publication (1)

  1. P-type ATPases: Many more enigmas left to solve. Palmgren M. J Biol Chem 299 105352 (2023)

Articles citing this publication (6)

  1. Lipid Transport by Candida albicans Dnf2 Is Required for Hyphal Growth and Virulence. Jain BK, Wagner AS, Reynolds TB, Graham TR. Infect Immun 90 e0041622 (2022)
  2. Activation and substrate specificity of the human P4-ATPase ATP8B1. Dieudonné T, Kümmerer F, Laursen MJ, Stock C, Flygaard RK, Khalid S, Lenoir G, Lyons JA, Lindorff-Larsen K, Nissen P. Nat Commun 14 7492 (2023)
  3. An antisteatosis response regulated by oleic acid through lipid droplet-mediated ERAD enhancement. Castillo-Quan JI, Steinbaugh MJ, Fernández-Cárdenas LP, Pohl NK, Wu Z, Zhu F, Moroz N, Teixeira V, Bland MS, Lehrbach NJ, Moronetti L, Teufl M, Blackwell TK. Sci Adv 9 eadc8917 (2023)
  4. Exploring the Phospholipid Transport Mechanism of ATP8A1-CDC50. Zhang H, Zhang Y, Xu P, Bai C. Biomedicines 11 546 (2023)
  5. Functional Analysis of the P-Type ATPases Apt2-4 from Cryptococcus neoformans by Heterologous Expression in Saccharomyces cerevisiae. Veit S, Laerbusch S, López-Marqués RL, Günther Pomorski T. J Fungi (Basel) 9 202 (2023)
  6. TOR complex 2 is a master regulator of plasma membrane homeostasis. Thorner J. Biochem J 479 1917-1940 (2022)


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