| Structural highlights
7ky9 is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | Electron Microscopy, Resolution 4.05Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ATC4_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 PubMed
The 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.
, PMID:33320091[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hua Z, Fatheddin P, Graham TR. An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal/vacuolar system. Mol Biol Cell. 2002 Sep;13(9):3162-77. PMID:12221123 doi:10.1091/mbc.e02-03-0172
- ↑ Pomorski T, Lombardi R, Riezman H, Devaux PF, van Meer G, Holthuis JC. Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid translocation across the yeast plasma membrane and serve a role in endocytosis. Mol Biol Cell. 2003 Mar;14(3):1240-54. PMID:12631737 doi:10.1091/mbc.e02-08-0501
- ↑ Jain BK, Roland BP, Graham TR. Exofacial membrane composition and lipid metabolism regulates plasma membrane P4-ATPase substrate specificity. J Biol Chem. 2020 Dec 25;295(52):17997-18009. PMID:33060204 doi:10.1074/jbc.RA120.014794
- ↑ Bai L, You Q, Jain BK, Duan HD, Kovach A, Graham TR, Li H. Transport mechanism of P4 ATPase phosphatidylcholine flippases. Elife. 2020 Dec 15;9:e62163. PMID:33320091 doi:10.7554/eLife.62163
- ↑ Bai L, You Q, Jain BK, Duan HD, Kovach A, Graham TR, Li H. Transport mechanism of P4 ATPase phosphatidylcholine flippases. Elife. 2020 Dec 15;9:e62163. PMID:33320091 doi:10.7554/eLife.62163
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