6k7j

Cryo-EM structure of the human P4-type flippase ATP8A1-CDC50 (E1-ATP state class1)

Loading... Status: waiting for Mol* initialization Structural highlights 6k7j is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.08Å Ligands: ACP, MAN, MG, NAG, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed In eukaryotic membranes, P4-ATPases mediate the translocation of phospholipids from the outer to inner leaflet and maintain lipid asymmetry, which is critical for membrane trafficking and signaling pathways. Here we report the cryo-EM structures of six distinct intermediates of the human ATP8A1-CDC50a hetero-complex, at 2.6-3.3 A resolutions, elucidating lipid translocation cycle of this P4-ATPase. ATP-dependent phosphorylation induces a large rotational movement of the actuator domain around the phosphorylation site in the phosphorylation domain, accompanied by lateral shifts of the first and second transmembrane helices, thereby allowing phosphatidylserine binding. The phospholipid head group passes through the hydrophilic cleft, while the acyl chain is exposed toward the lipid environment. These findings advance our understanding of the flippase mechanism and the disease-associated mutants of P4-ATPases. Cryo-EM structures capture the transport cycle of the P4-ATPase flippase.,Hiraizumi M, Yamashita K, Nishizawa T, Nureki O Science. 2019 Aug 15. pii: science.aay3353. doi: 10.1126/science.aay3353. PMID:31416931 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ATPase 3D structures

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