7ky8
From Proteopedia
Structure of the S. cerevisiae phosphatidylcholine flippase Dnf2-Lem3 complex in the E1-ATP state
Structural highlights
FunctionATC4_YEAST Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide, phosphatidylcholine, phosphatidylethanolamine, and small amounts of phosphatidylserine from the lumenal to the cytosolic leaflet of the cell membrane and ensures the maintenance of asymmetric distribution of phospholipids (PubMed:12631737, PubMed:33060204, PubMed:33320091). Does not appear to transport sphingomyelin, inositol phosphoceramide or phosphatidic acid (PubMed:12631737, PubMed:33320091). Required for efficient endocytosis (PubMed:12631737). Required for protein transport from Golgi to vacuoles (PubMed:12221123).[1] [2] [3] [4] Publication Abstract from PubMedThe P4 ATPases use ATP hydrolysis to transport large lipid substrates across lipid bilayers. The structures of the endosome- and Golgi-localized phosphatidylserine flippases-such as the yeast Drs2 and human ATP8A1-have recently been reported. However, a substrate-binding site on the cytosolic side has not been found, and the transport mechanisms of P4 ATPases with other substrates are unknown. Here, we report structures of the S. cerevisiae Dnf1-Lem3 and Dnf2-Lem3 complexes. We captured substrate phosphatidylcholine molecules on both the exoplasmic and cytosolic sides and found that they have similar structures. Unexpectedly, Lem3 contributes to substrate binding. The conformational transitions of these phosphatidylcholine transporters match those of the phosphatidylserine transporters, suggesting a conserved mechanism among P4 ATPases. Dnf1/Dnf2 have a unique P domain helix-turn-helix insertion that is important for function. Therefore, P4 ATPases may have retained an overall transport mechanism while evolving distinct features for different lipid substrates. Transport mechanism of P4 ATPase phosphatidylcholine flippases.,Bai L, You Q, Jain BK, Duan HD, Kovach A, Graham TR, Li H Elife. 2020 Dec 15;9:e62163. doi: 10.7554/eLife.62163. PMID:33320091[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Saccharomyces cerevisiae S288C | Bai L | Duan HD | Graham TR | Jain BK | Kovach A | Li H | You Q
