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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 | |||||||||
Components |
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Keywords | LIPID TRANSPORT/TRANSLOCASE / auto-inhibited / phosphorylated / lipid flippase / LIPID TRANSPORT / LIPID TRANSPORT-TRANSLOCASE complex | |||||||||
Function / homology | Function and homology information vestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / positive regulation of phospholipid translocation / phosphatidylcholine flippase activity / aminophospholipid transport / aminophospholipid flippase activity / phosphatidylserine flippase activity / protein localization to endosome / inner ear receptor cell development ...vestibulocochlear nerve formation / regulation of plasma membrane organization / regulation of microvillus assembly / positive regulation of phospholipid translocation / phosphatidylcholine flippase activity / aminophospholipid transport / aminophospholipid flippase activity / phosphatidylserine flippase activity / protein localization to endosome / inner ear receptor cell development / ATPase-coupled intramembrane lipid transporter activity / phospholipid-translocating ATPase complex / phosphatidylserine floppase activity / positive regulation of protein exit from endoplasmic reticulum / xenobiotic transmembrane transport / phosphatidylcholine floppase activity / stereocilium / apical protein localization / bile acid metabolic process / P-type phospholipid transporter / cardiolipin binding / phospholipid translocation / bile acid and bile salt transport / azurophil granule membrane / transport vesicle membrane / Golgi organization / Ion transport by P-type ATPases / specific granule membrane / regulation of chloride transport / sensory perception of sound / trans-Golgi network / 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 / Golgi apparatus / magnesium ion binding / endoplasmic reticulum / 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: 2022 Title: 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. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-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 (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-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 |
#5: Sugar |
-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 |
-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 % |
-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) |
-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 |