+Open data
-Basic information
Entry | Database: PDB / ID: 7w02 | ||||||
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Title | Cryo-EM structure of ATP-bound ABCA3 | ||||||
Components | Phospholipid-transporting ATPase ABCA3 | ||||||
Keywords | TRANSLOCASE / ABC transporter / MEMBRANE PROTEIN | ||||||
Function / homology | Function and homology information lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / positive regulation of protein homooligomerization / regulation of phosphatidylcholine metabolic process / phosphatidylcholine transfer activity / lamellar body / positive regulation of phospholipid transport / xenobiotic export from cell ...lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / positive regulation of protein homooligomerization / regulation of phosphatidylcholine metabolic process / phosphatidylcholine transfer activity / lamellar body / positive regulation of phospholipid transport / xenobiotic export from cell / alveolar lamellar body / organelle assembly / phosphatidylcholine flippase activity / positive regulation of phospholipid efflux / lipid transporter activity / ABC transporters in lipid homeostasis / phosphatidylglycerol metabolic process / regulation of lipid biosynthetic process / phosphatidylcholine metabolic process / xenobiotic transmembrane transport / phospholipid homeostasis / Surfactant metabolism / multivesicular body membrane / phospholipid transport / ABC-type xenobiotic transporter / protein metabolic process / surfactant homeostasis / P-type phospholipid transporter / ABC-type xenobiotic transporter activity / xenobiotic transport / lipid transport / positive regulation of cholesterol efflux / ATPase-coupled transmembrane transporter activity / response to glucocorticoid / lung development / cytoplasmic vesicle membrane / late endosome / membrane => GO:0016020 / response to xenobiotic stimulus / lysosomal membrane / intracellular membrane-bounded organelle / ATP hydrolysis activity / extracellular space / ATP binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Xie, T. / Zhang, Z.K. / Yue, J. / Gong, X. | ||||||
Funding support | 1items
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Citation | Journal: Sci Adv / Year: 2022 Title: Cryo-EM structures of the human surfactant lipid transporter ABCA3. Authors: Tian Xie / Zike Zhang / Jian Yue / Qi Fang / Xin Gong / Abstract: The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most ...The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most frequent causes of inherited surfactant dysfunction disorders. Despite two decades of research, in vitro biochemical and structural studies of ABCA3 are still lacking. Here, we report the cryo-EM structures of human ABCA3 in two distinct conformations, both at resolution of 3.3 Å. In the absence of ATP, ABCA3 adopts a "lateral-opening" conformation with the lateral surfaces of transmembrane domains (TMDs) exposed to the membrane and features two positively charged cavities within the TMDs as potential substrate binding sites. ATP binding induces pronounced conformational changes, resulting in the collapse of the potential substrate binding cavities. Our results help to rationalize the disease-causing mutations in human ABCA3 and suggest a conserved "lateral access and extrusion" mechanism for both lipid export and import mediated by ABCA transporters. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7w02.cif.gz | 286.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7w02.ent.gz | 229.2 KB | Display | PDB format |
PDBx/mmJSON format | 7w02.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w0/7w02 ftp://data.pdbj.org/pub/pdb/validation_reports/w0/7w02 | HTTPS FTP |
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-Related structure data
Related structure data | 32234MC 7w01C C: citing same article (ref.) M: map data used to model this data |
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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
#1: Protein | Mass: 196511.688 Da / Num. of mol.: 1 / Mutation: E690Q, E1540Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ABCA3, ABC3 / Production host: Homo sapiens (human) References: UniProt: Q99758, P-type phospholipid transporter, ABC-type xenobiotic transporter | ||||||
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#2: Chemical | #3: Chemical | #4: Sugar | Has ligand of interest | Y | |
-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: ABCA3 / Type: COMPLEX / Entity ID: #1 / 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 |
-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 FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.1_3865: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 80575 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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