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- PDB-6k7i: Cryo-EM structure of the human P4-type flippase ATP8A1-CDC50 (E1-... -
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Basic information
Entry | Database: PDB / ID: 6k7i | ||||||||||||
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Title | Cryo-EM structure of the human P4-type flippase ATP8A1-CDC50 (E1-ATP state class2) | ||||||||||||
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![]() | MEMBRANE PROTEIN / flippase | ||||||||||||
Function / homology | ![]() aminophospholipid translocation / positive regulation of phospholipid translocation / aminophospholipid flippase activity / aminophospholipid transport / chromaffin granule membrane / phosphatidylserine flippase activity / protein localization to endosome / phospholipid-translocating ATPase complex / ATPase-coupled intramembrane lipid transporter activity / phosphatidylserine floppase activity ...aminophospholipid translocation / positive regulation of phospholipid translocation / aminophospholipid flippase activity / aminophospholipid transport / chromaffin granule membrane / phosphatidylserine flippase activity / protein localization to endosome / phospholipid-translocating ATPase complex / ATPase-coupled intramembrane lipid transporter activity / phosphatidylserine floppase activity / positive regulation of protein exit from endoplasmic reticulum / xenobiotic transmembrane transport / ATPase-coupled monoatomic cation transmembrane transporter activity / P-type phospholipid transporter / phospholipid translocation / transport vesicle membrane / azurophil granule membrane / organelle membrane / Ion transport by P-type ATPases / transport across blood-brain barrier / endomembrane system / specific granule membrane / monoatomic ion transmembrane transport / learning / trans-Golgi network / synaptic vesicle membrane / positive regulation of neuron projection development / late endosome membrane / early endosome membrane / cytoplasmic vesicle / positive regulation of cell migration / apical plasma membrane / intracellular membrane-bounded organelle / Neutrophil degranulation / structural molecule activity / Golgi apparatus / magnesium ion binding / endoplasmic reticulum / ATP hydrolysis activity / extracellular exosome / ATP binding / membrane / plasma membrane / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.22 Å | ||||||||||||
![]() | Hiraizumi, M. / Yamashita, K. / Nishizawa, T. / Nureki, O. | ||||||||||||
![]() | ![]() Title: Cryo-EM structures capture the transport cycle of the P4-ATPase flippase. Authors: Masahiro Hiraizumi / Keitaro Yamashita / Tomohiro Nishizawa / Osamu Nureki / ![]() 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 ...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. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 255.8 KB | Display | ![]() |
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PDB format | ![]() | 198.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9934MC ![]() 9931C ![]() 9932C ![]() 9933C ![]() 9935C ![]() 9936C ![]() 9937C ![]() 9938C ![]() 9939C ![]() 9940C ![]() 9941C ![]() 9942C ![]() 6k7gC ![]() 6k7hC ![]() 6k7jC ![]() 6k7kC ![]() 6k7lC ![]() 6k7mC ![]() 6k7nC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Unaligned movies for E2P class 1,2,3 [micrographs - multiframe] Data #2: Unaligned movies for E2Pi-PL and E1P [micrographs - multiframe] Data #3: Unaligned movies for E1P-ADP [micrographs - multiframe] Data #4: Unaligned movies for E1 class1,2,3 [micrographs - multiframe] Data #5: Unaligned movies for E1-ATP class 1,2,3 [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules AC
#1: Protein | Mass: 130537.852 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: Q59EX4, UniProt: Q9Y2Q0*PLUS, P-type phospholipid transporter |
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#2: Protein | Mass: 40727.527 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 2 types, 3 molecules ![](data/chem/img/NAG.gif)
#3: Polysaccharide | alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#5: Sugar |
-Non-polymers , 2 types, 2 molecules ![](data/chem/img/ACP.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/Y01.gif)
#4: Chemical | ChemComp-ACP / |
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#6: Chemical | ChemComp-Y01 / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: ATP8A1-CDC50a / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 139945 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
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