Evolution and a revised nomenclature of P4 ATPases, a eukaryotic family of lipid flippases

Palmgren, Michael G.; Østerberg, Jeppe Thulin; Nintemann, Sebastian J.; Poulsen, Lisbeth R.; López‐Marqués, Rosa L.

doi:10.1016/j.bbamem.2019.02.006

Cited by 51 publications

(44 citation statements)

References 60 publications

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“…However, this mirrored property of eukaryotic clades provides evidence that both P-type ATPase genes were duplicated very early in eukaryotic evolution, before the divergence of the present eukaryotic supergroups (Figs 1,2,4 and 5). A similar duplication event has recently been observed in P4 ATPase flippases, a third P-type ATPase subfamily (Palmgren et al 2019).…”

Section: Signs Of Gene Duplications At the Time Of The Last Common Eusupporting

confidence: 69%

Evolution of P2A and P5A ATPases: ancient gene duplications and the red algal connection to green plants revisited

Palmgren

Sørensen

Hallström

et al. 2019

Physiologia Plantarum

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In a search for slowly evolving nuclear genes that may cast light on the deep evolution of plants, we carried out phylogenetic analyses of two well‐characterized subfamilies of P‐type pumps (P2A and P5A ATPases) from representative branches of the eukaryotic tree of life. Both P‐type ATPase genes were duplicated very early in eukaryotic evolution and before the divergence of the present eukaryotic supergroups. Synapomorphies identified in the sequences provide evidence that green plants and red algae are more distantly related than are green plants and eukaryotic supergroups in which secondary or tertiary plastids are common, such as several groups belonging to the clade that includes Stramenopiles, Alveolata, Rhizaria, Cryptophyta and Haptophyta (SAR). We propose that red algae branched off soon after the first photosynthesizing eukaryote had acquired a primary plastid, while in another lineage that led to SAR, the primary plastid was lost but, in some cases, regained as a secondary or tertiary plastid.

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Section: Signs Of Gene Duplications At the Time Of The Last Common Eusupporting

confidence: 69%

Evolution of P2A and P5A ATPases: ancient gene duplications and the red algal connection to green plants revisited

Palmgren

Sørensen

Hallström

et al. 2019

Physiologia Plantarum

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“…The yeast lipid flippase Drs2p-Cdc50p is primarily found in the trans-Golgi network and is involved in protein trafficking between that network, the plasma membrane, and endosomes 1 . Drs2p belongs to a large family of Type IV P-type ATPases (P4 ATPases) 2 . These enzymes translocate specific phospholipids from the extracellular side of the plasma membrane or from the lumenal side of internal organelles to the cytosolic side, creating and maintaining lipid compositional asymmetry in eukaryotic cell membranes.…”

Section: Introductionmentioning

confidence: 99%

Autoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p

et al. 2019

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The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry. The enzyme complex exists in an autoinhibited form in the absence of an activator and is specifically activated by phosphatidylinositol-4-phosphate (PI4P), although the underlying mechanisms have been unclear. Here we report the cryo-EM structures of intact Drs2p-Cdc50p isolated from S. cerevisiae in apo form and in the PI4P-activated form at 2.8 Å and 3.3 Å resolution, respectively. The structures reveal that the Drs2p C-terminus lines a long groove in the cytosolic regulatory region to inhibit the flippase activity. PIP4 binding in a cytosol-proximal membrane region triggers a 90° rotation of a cytosolic helix switch that is located just upstream of the inhibitory C-terminal peptide. The rotation of the helix switch dislodges the C-terminus from the regulatory region, activating the flippase.

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“…We and others previously showed that interaction of most P4‐ATPases (P4A clade, based on a revised phylogenetic analysis of P4‐ATPases), except for ATP9A and ATP9B (P4B clade), with CDC50 proteins is crucial for their cellular localization . Mutation of the aspartate residue within the DKTGT sequence motif does not allow some P4‐ATPases to exit the endoplasmic reticulum (ER) and probably inhibits their interaction with CDC50 proteins .…”

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confidence: 99%

ATPase reaction cycle of P4‐ATPases affects their transport from the endoplasmic reticulum

et al. 2019

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P4‐ATPases belonging to the P‐type ATPase superfamily mediate active transport of phospholipids across cellular membranes. Most P4‐ATPases, except ATP9A and ATP9B proteins, form heteromeric complexes with CDC50 proteins, which are required for transport of P4‐ATPases from the endoplasmic reticulum (ER) to their final destinations. P‐type ATPases form autophosphorylated intermediates during the ATPase reaction cycle. However, the association of the catalytic cycle of P4‐ATPases with their transport from the ER and their cellular localization has not been studied. Here, we show that transport of ATP9 and ATP11 proteins as well as that of ATP10A from the ER depends on the ATPase catalytic cycle, suggesting that conformational changes in P4‐ATPases during the catalytic cycle are crucial for their transport from the ER.

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Evolution and a revised nomenclature of P4 ATPases, a eukaryotic family of lipid flippases

Cited by 51 publications

References 60 publications

Evolution of P2A and P5A ATPases: ancient gene duplications and the red algal connection to green plants revisited

Evolution of P2A and P5A ATPases: ancient gene duplications and the red algal connection to green plants revisited

Autoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p

ATPase reaction cycle of P4‐ATPases affects their transport from the endoplasmic reticulum

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