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Yorodumi- PDB-7vgi: Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50A in ... -
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Basic information
| Entry | Database: PDB / ID: 7vgi | |||||||||
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| Title | Cryo-EM structure of the human P4-type flippase ATP8B1-CDC50A in the auto-inhibited E2P state | |||||||||
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Keywords | LIPID TRANSPORT/TRANSLOCASE / auto-inhibited / phosphorylated / lipid flippase / LIPID TRANSPORT / LIPID TRANSPORT-TRANSLOCASE complex | |||||||||
| Function / homology | Function and homology informationvestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / positive regulation of phospholipid translocation / phosphatidylcholine flippase activity / aminophospholipid flippase activity / aminophospholipid transport / phosphatidylserine flippase activity / protein localization to endosome / phospholipid-translocating ATPase complex ...vestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / positive regulation of phospholipid translocation / phosphatidylcholine flippase activity / aminophospholipid flippase activity / aminophospholipid transport / phosphatidylserine flippase activity / protein localization to endosome / phospholipid-translocating ATPase complex / positive regulation of protein exit from endoplasmic reticulum / phosphatidylserine floppase activity / ATPase-coupled intramembrane lipid transporter activity / phosphatidylcholine floppase activity / xenobiotic transmembrane transport / bile acid metabolic process / stereocilium / cardiolipin binding / P-type phospholipid transporter / inner ear receptor cell development / apical protein localization / phospholipid translocation / azurophil granule membrane / transport vesicle membrane / bile acid and bile salt transport / Golgi organization / Ion transport by P-type ATPases / specific granule membrane / regulation of chloride transport / trans-Golgi network / sensory perception of sound / positive regulation of neuron projection development / late endosome membrane / early endosome membrane / monoatomic ion transmembrane transport / nuclear body / apical plasma membrane / negative regulation of DNA-templated transcription / Neutrophil degranulation / structural molecule activity / magnesium ion binding / endoplasmic reticulum / Golgi apparatus / ATP hydrolysis activity / nucleoplasm / ATP binding / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.36 Å | |||||||||
Authors | Chen, M.T. / Chen, Y. | |||||||||
| Funding support | China, 2items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022Title: Structural insights into the activation of autoinhibited human lipid flippase ATP8B1 upon substrate binding. Authors: Meng-Ting Cheng / Yu Chen / Zhi-Peng Chen / Xin Liu / Zhiyong Zhang / Yuxing Chen / Wen-Tao Hou / Cong-Zhao Zhou / ![]() Abstract: SignificanceATP8B1 is a P4 ATPase that maintains membrane asymmetry by transporting phospholipids across the cell membrane. Disturbance of lipid asymmetry will lead to the imbalance of the cell ...SignificanceATP8B1 is a P4 ATPase that maintains membrane asymmetry by transporting phospholipids across the cell membrane. Disturbance of lipid asymmetry will lead to the imbalance of the cell membrane and eventually, cell death. Thus, defects in ATP8B1 are usually associated with severe human diseases, such as intrahepatic cholestasis. The present structures of ATP8B1 complexed with its auxiliary noncatalytic partners CDC50A and CDC50B reveal an autoinhibited state of ATP8B1 that could be released upon substrate binding. Moreover, release of this autoinhibition could be facilitated by the bile acids, which are key factors that alter the membrane asymmetry of hepatocytes. This enabled us to figure out a feedback loop of bile acids and lipids across the cell membrane. | |||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 7vgi.cif.gz | 283.6 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb7vgi.ent.gz | 224.4 KB | Display | PDB format |
| PDBx/mmJSON format | 7vgi.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 7vgi_validation.pdf.gz | 982.5 KB | Display | wwPDB validaton report |
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| Full document | 7vgi_full_validation.pdf.gz | 1000.7 KB | Display | |
| Data in XML | 7vgi_validation.xml.gz | 45.5 KB | Display | |
| Data in CIF | 7vgi_validation.cif.gz | 68.3 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vg/7vgi ftp://data.pdbj.org/pub/pdb/validation_reports/vg/7vgi | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 31970MC ![]() 7vghC ![]() 7vgjC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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| 1 |
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Components
-Protein , 2 types, 2 molecules AB
| #1: Protein | Mass: 41845.746 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TMEM30A, C6orf67, CDC50A / Production host: Homo sapiens (human) / References: UniProt: Q9NV96 |
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| #2: Protein | Mass: 148538.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ATP8B1, ATPIC, FIC1, PFIC / Production host: Homo sapiens (human)References: UniProt: O43520, P-type phospholipid transporter |
-Sugars , 3 types, 4 molecules 
| #3: Polysaccharide | 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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| #4: 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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-Non-polymers , 1 types, 1 molecules 
| #6: Chemical | ChemComp-MG / |
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-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: ATP8B1-CDC50A complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE / Humidity: 100 % |
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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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD |
| Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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| 3D reconstruction | Resolution: 3.36 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 182618 / Symmetry type: POINT |
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About Yorodumi



Homo sapiens (human)
China, 2items
Citation




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gel filtration
