+
Open data
-
Basic information
Entry | Database: PDB / ID: 7w01 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of nucleotide-free ABCA3 | ||||||
![]() | Phospholipid-transporting ATPase ABCA3 | ||||||
![]() | TRANSLOCASE / ABC transporter / MEMBRANE PROTEIN | ||||||
Function / homology | ![]() positive regulation of protein homooligomerization / lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / regulation of phosphatidylcholine metabolic process / phosphatidylcholine transfer activity / lamellar body / positive regulation of phospholipid transport / xenobiotic export from cell ...positive regulation of protein homooligomerization / lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / 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 / ABC transporters in lipid homeostasis / phosphatidylglycerol metabolic process / regulation of lipid biosynthetic process / phosphatidylcholine metabolic process / positive regulation of phospholipid efflux / xenobiotic transmembrane transport / Surfactant metabolism / phospholipid homeostasis / lipid transporter activity / multivesicular body membrane / phospholipid transport / protein metabolic process / ABC-type xenobiotic transporter / P-type phospholipid transporter / xenobiotic transport / surfactant homeostasis / ABC-type xenobiotic transporter activity / lipid transport / ATPase-coupled transmembrane transporter activity / positive regulation of cholesterol efflux / 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 | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Xie, T. / Zhang, Z.K. / Yue, J. / Gong, X. | ||||||
Funding support | 1items
| ||||||
![]() | ![]() 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 |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 293.4 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 235.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 32233MC ![]() 7w02C M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 196513.656 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: Q99758, P-type phospholipid transporter, ABC-type xenobiotic transporter | ||||||
---|---|---|---|---|---|---|---|
#2: Sugar | #3: Chemical | #4: Chemical | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: ABCA3 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
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 |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
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 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 111435 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|