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6K7L

Cryo-EM structure of the human P4-type flippase ATP8A1-CDC50 (E2P state class2)

Summary for 6K7L
Entry DOI10.2210/pdb6k7l/pdb
EMDB information9939
DescriptorPhospholipid-transporting ATPase, Cell cycle control protein 50A, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
Functional Keywordsflippase, membrane protein
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains2
Total formula weight172871.38
Authors
Hiraizumi, M.,Yamashita, K.,Nishizawa, T.,Nureki, O. (deposition date: 2019-06-07, release date: 2019-08-28, Last modification date: 2021-02-03)
Primary citationHiraizumi, M.,Yamashita, K.,Nishizawa, T.,Nureki, O.
Cryo-EM structures capture the transport cycle of the P4-ATPase flippase.
Science, 365:1149-1155, 2019
Cited by
PubMed Abstract: In eukaryotic membranes, type IV P-type adenosine triphosphatases (P4-ATPases) mediate the translocation of phospholipids from the outer to the inner leaflet and maintain lipid asymmetry, which is critical for membrane trafficking and signaling pathways. Here, we report the cryo-electron microscopy structures of six distinct intermediates of the human ATP8A1-CDC50a heterocomplex at resolutions of 2.6 to 3.3 angstroms, elucidating the 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.
PubMed: 31416931
DOI: 10.1126/science.aay3353
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.83 Å)
Structure validation

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